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    Clinical Trial Results:
    A Phase II/III Partially Double-Blinded, Randomised, Multinational, Active-Controlled Study in Both Previously Vaccinated and Unvaccinated Adults to Determine the Safety and Immunogenicity of AZD2816, a Vaccine for the Prevention of COVID-19 Caused by Variant Strains of SARS-CoV-2

    Summary
    EudraCT number
    2021-002530-17
    Trial protocol
    PL  
    Global end of trial date
    02 Aug 2022

    Results information
    Results version number
    v2(current)
    This version publication date
    18 May 2024
    First version publication date
    13 Aug 2023
    Other versions
    v1
    Version creation reason

    Trial information

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    Trial identification
    Sponsor protocol code
    D7220C00001
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT04973449
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    MedImmune, LLC
    Sponsor organisation address
    One MedImmune Way, Gaithersburg, Maryland, United States, 20878
    Public contact
    Global Clinical Lead, AstraZeneca Clinical study Information Center, +1 8772409479, information.center@astrazeneca.com
    Scientific contact
    Global Clinical Lead, AstraZeneca Clinical study Information Center, +1 8772409479, information.center@astrazeneca.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    29 Sep 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    02 Aug 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Primary objectives of the study are in seronegative participants as follows: 1. To characterize safety and tolerability of a 2-dose primary vaccination with AZD2816 (4-week dosing interval [4]) in previously unvaccinated participants and one booster dose of AZD2816 in participants previously vaccinated with AZD1222 or messenger ribronucleic acid (mRNA) primary series vaccination. 2. To determine the non-inferiority of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) neutralizing antibody (nAb) geometric mean titre (GMT) response and seroresponse: (a) Against B.1.351 variant elicited by a 2-dose primary vaccination with AZD2816 (4) versus (vs) original Wuhan-Hu-1 strain elicited by a 2-dose primary vaccination with AZD1222 (4). (b) Against original Wuhan-Hu-1 strain elicited by AZD1222 booster dose in participants previously vaccinated with AZD1222 or mRNA primary vaccination vs 2-dose AZD1222 vaccination administered to previously unvaccinated participants.
    Protection of trial subjects
    The conduct of this clinical study met all local and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and are consistent with International Conference on Harmonization guideline: Good Clinical Practice, and applicable regulatory requirements. Participants signed an informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    27 Jun 2021
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Brazil: 966
    Country: Number of subjects enrolled
    South Africa: 464
    Country: Number of subjects enrolled
    Poland: 58
    Country: Number of subjects enrolled
    United Kingdom: 1346
    Worldwide total number of subjects
    2834
    EEA total number of subjects
    58
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    2251
    From 65 to 84 years
    571
    85 years and over
    12

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    A total of 2843 participants were randomized in this study of which 2834 participants were treated (9 participants were randomized but not treated). Results are presented for 2834 treated participants only.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Monitor, Data analyst, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Primary Vaccination Cohort:- AZD1222 (4)
    Arm description
    Previously unvaccinated participants received intramuscular (IM) AZD1222 5*10^10 viral particles (vp) on Days 1 and 29 (4-week dosing interval).
    Arm type
    Experimental

    Investigational medicinal product name
    AZD1222
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Intramuscular (IM) AZD1222 5*10^10 viral particles (vp) on Days 1 and 29.

    Arm title
    Primary Vaccination Cohort:- AZD2816 (4)
    Arm description
    Previously unvaccinated participants received IM AZD2816 5*10^10 vp on Days 1 and 29 (4-week dosing interval).
    Arm type
    Experimental

    Investigational medicinal product name
    AZD2816
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    IM AZD2816 5*10^10 vp on Days 1 and 29.

    Arm title
    Primary Vaccination Cohort:- AZD1222 + AZD2816 (4)
    Arm description
    Previously unvaccinated participants received IM AZD1222 5*10^10 vp on Day 1 and IM AZD2816 5*10^10 vp on Day 29 (4-week dosing interval).
    Arm type
    Experimental

    Investigational medicinal product name
    AZD2816
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    IM AZD2816 5*10^10 vp on Day 29.

    Investigational medicinal product name
    AZD1222
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    IM AZD1222 5*10^10 vp on Day 1.

    Arm title
    Primary Vaccination Cohort:- AZD2816 (12)
    Arm description
    Previously unvaccinated participants received IM AZD2816 5*10^10 vp on Days 1 and 85 (12-week dosing interval).
    Arm type
    Experimental

    Investigational medicinal product name
    AZD2816
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    IM AZD2816 5*10^10 vp on Days 1 and 85.

    Arm title
    Booster Cohort:- AZD1222:AZD1222
    Arm description
    Participants, who previously received 2 doses of AZD1222 vaccine according to the authorized dose and dosing regimen, with second dose administered at least 90 days prior to study treatment, received booster dose of IM AZD1222 5*10^10 vp on Day 1.
    Arm type
    Experimental

    Investigational medicinal product name
    AZD1222
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    IM AZD1222 5*10^10 vp on Day 1.

    Arm title
    Booster Cohort:- AZD1222:AZD2816
    Arm description
    Participants, who previously received 2 doses of AZD1222 vaccine according to the authorized dose and dosing regimen, with second dose administered at least 90 days prior to study treatment, received booster dose of IM AZD2816 5*10^10 vp on Day 1.
    Arm type
    Experimental

    Investigational medicinal product name
    AZD2816
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    IM AZD2816 5*10^10 vp on Day 1.

    Arm title
    Booster Cohort:- mRNA:AZD1222
    Arm description
    Participants, who previously received 2 doses of approved mRNA based vaccine according to the authorized dose and dosing regimen, with second dose administered at least 90 days prior to study treatment, received booster dose of IM AZD1222 5*10^10 vp on Day 1.
    Arm type
    Experimental

    Investigational medicinal product name
    AZD1222
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    IM AZD1222 5*10^10 vp on Day 1.

    Arm title
    Booster Cohort:- mRNA:AZD2816
    Arm description
    Participants, who previously received 2 doses of approved mRNA based vaccine according to the authorized dose and dosing regimen, with second dose administered at least 90 days prior to study treatment, received booster dose of IM AZD2816 5*10^10 vp on Day 1.
    Arm type
    Experimental

    Investigational medicinal product name
    AZD2816
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    IM AZD2816 5*10^10 vp on Day 1.

    Number of subjects in period 1
    Primary Vaccination Cohort:- AZD1222 (4) Primary Vaccination Cohort:- AZD2816 (4) Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) Primary Vaccination Cohort:- AZD2816 (12) Booster Cohort:- AZD1222:AZD1222 Booster Cohort:- AZD1222:AZD2816 Booster Cohort:- mRNA:AZD1222 Booster Cohort:- mRNA:AZD2816
    Started
    409
    413
    411
    208
    373
    377
    322
    321
    Completed
    389
    393
    391
    189
    359
    366
    303
    308
    Not completed
    20
    20
    20
    19
    14
    11
    19
    13
         Adverse event, serious fatal
    1
    -
    -
    -
    -
    1
    -
    -
         Consent withdrawn by subject
    3
    3
    2
    5
    5
    4
    7
    5
         Unspecified
    1
    1
    2
    1
    4
    -
    2
    2
         Lost to follow-up
    15
    16
    16
    13
    5
    6
    10
    6

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Primary Vaccination Cohort:- AZD1222 (4)
    Reporting group description
    Previously unvaccinated participants received intramuscular (IM) AZD1222 5*10^10 viral particles (vp) on Days 1 and 29 (4-week dosing interval).

    Reporting group title
    Primary Vaccination Cohort:- AZD2816 (4)
    Reporting group description
    Previously unvaccinated participants received IM AZD2816 5*10^10 vp on Days 1 and 29 (4-week dosing interval).

    Reporting group title
    Primary Vaccination Cohort:- AZD1222 + AZD2816 (4)
    Reporting group description
    Previously unvaccinated participants received IM AZD1222 5*10^10 vp on Day 1 and IM AZD2816 5*10^10 vp on Day 29 (4-week dosing interval).

    Reporting group title
    Primary Vaccination Cohort:- AZD2816 (12)
    Reporting group description
    Previously unvaccinated participants received IM AZD2816 5*10^10 vp on Days 1 and 85 (12-week dosing interval).

    Reporting group title
    Booster Cohort:- AZD1222:AZD1222
    Reporting group description
    Participants, who previously received 2 doses of AZD1222 vaccine according to the authorized dose and dosing regimen, with second dose administered at least 90 days prior to study treatment, received booster dose of IM AZD1222 5*10^10 vp on Day 1.

    Reporting group title
    Booster Cohort:- AZD1222:AZD2816
    Reporting group description
    Participants, who previously received 2 doses of AZD1222 vaccine according to the authorized dose and dosing regimen, with second dose administered at least 90 days prior to study treatment, received booster dose of IM AZD2816 5*10^10 vp on Day 1.

    Reporting group title
    Booster Cohort:- mRNA:AZD1222
    Reporting group description
    Participants, who previously received 2 doses of approved mRNA based vaccine according to the authorized dose and dosing regimen, with second dose administered at least 90 days prior to study treatment, received booster dose of IM AZD1222 5*10^10 vp on Day 1.

    Reporting group title
    Booster Cohort:- mRNA:AZD2816
    Reporting group description
    Participants, who previously received 2 doses of approved mRNA based vaccine according to the authorized dose and dosing regimen, with second dose administered at least 90 days prior to study treatment, received booster dose of IM AZD2816 5*10^10 vp on Day 1.

    Reporting group values
    Primary Vaccination Cohort:- AZD1222 (4) Primary Vaccination Cohort:- AZD2816 (4) Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) Primary Vaccination Cohort:- AZD2816 (12) Booster Cohort:- AZD1222:AZD1222 Booster Cohort:- AZD1222:AZD2816 Booster Cohort:- mRNA:AZD1222 Booster Cohort:- mRNA:AZD2816 Total
    Number of subjects
    409 413 411 208 373 377 322 321 2834
    Age categorical
    Units: Subjects
        In utero
    0 0 0 0 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0 0 0 0 0 0 0 0
        Newborns (0-27 days)
    0 0 0 0 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    0 0 0 0 0 0 0 0 0
        Children (2-11 years)
    0 0 0 0 0 0 0 0 0
        Adolescents (12-17 years)
    0 0 0 0 0 0 0 0 0
        Adults (18-64 years)
    392 391 394 198 199 203 238 236 2251
        From 65-84 years
    16 22 17 10 173 173 83 77 571
        85 years and over
    1 0 0 0 1 1 1 8 12
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    29.1 ± 12.48 29.7 ± 12.95 28.0 ± 12.23 28.8 ± 12.98 59.7 ± 13.72 60.4 ± 13.30 55.3 ± 13.19 55.9 ± 13.73 -
    Sex: Female, Male
    Units: Participants
        Female
    171 169 166 85 172 172 197 192 1324
        Male
    238 244 245 123 201 205 125 129 1510
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    4 0 2 2 0 0 0 0 8
        Asian
    3 5 4 0 10 14 8 13 57
        Native Hawaiian or Other Pacific Islander
    0 0 0 0 0 0 0 0 0
        Black or African American
    202 192 214 98 2 1 3 2 714
        White
    161 166 151 86 325 328 290 288 1795
        More than one race
    11 23 10 6 0 1 2 0 53
        Unknown or Not Reported
    28 27 30 16 36 33 19 18 207
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    239 246 257 131 8 10 4 6 901
        Not Hispanic or Latino
    143 148 137 70 322 331 291 292 1734
        Unknown or Not Reported
    27 19 17 7 43 36 27 23 199

    End points

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    End points reporting groups
    Reporting group title
    Primary Vaccination Cohort:- AZD1222 (4)
    Reporting group description
    Previously unvaccinated participants received intramuscular (IM) AZD1222 5*10^10 viral particles (vp) on Days 1 and 29 (4-week dosing interval).

    Reporting group title
    Primary Vaccination Cohort:- AZD2816 (4)
    Reporting group description
    Previously unvaccinated participants received IM AZD2816 5*10^10 vp on Days 1 and 29 (4-week dosing interval).

    Reporting group title
    Primary Vaccination Cohort:- AZD1222 + AZD2816 (4)
    Reporting group description
    Previously unvaccinated participants received IM AZD1222 5*10^10 vp on Day 1 and IM AZD2816 5*10^10 vp on Day 29 (4-week dosing interval).

    Reporting group title
    Primary Vaccination Cohort:- AZD2816 (12)
    Reporting group description
    Previously unvaccinated participants received IM AZD2816 5*10^10 vp on Days 1 and 85 (12-week dosing interval).

    Reporting group title
    Booster Cohort:- AZD1222:AZD1222
    Reporting group description
    Participants, who previously received 2 doses of AZD1222 vaccine according to the authorized dose and dosing regimen, with second dose administered at least 90 days prior to study treatment, received booster dose of IM AZD1222 5*10^10 vp on Day 1.

    Reporting group title
    Booster Cohort:- AZD1222:AZD2816
    Reporting group description
    Participants, who previously received 2 doses of AZD1222 vaccine according to the authorized dose and dosing regimen, with second dose administered at least 90 days prior to study treatment, received booster dose of IM AZD2816 5*10^10 vp on Day 1.

    Reporting group title
    Booster Cohort:- mRNA:AZD1222
    Reporting group description
    Participants, who previously received 2 doses of approved mRNA based vaccine according to the authorized dose and dosing regimen, with second dose administered at least 90 days prior to study treatment, received booster dose of IM AZD1222 5*10^10 vp on Day 1.

    Reporting group title
    Booster Cohort:- mRNA:AZD2816
    Reporting group description
    Participants, who previously received 2 doses of approved mRNA based vaccine according to the authorized dose and dosing regimen, with second dose administered at least 90 days prior to study treatment, received booster dose of IM AZD2816 5*10^10 vp on Day 1.

    Subject analysis set title
    Historical Control
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    A sub-population of participants from Study D8110C00001 (NCT04516746), who were matched with the AZD1222 cohort in this study based on age, body mass index, sex, and presence of baseline comorbidities are included and selected from those treated with 2 doses of AZD1222, gave informed consent, had no protocol deviations judged to have the potential to interfere with the generation or interpretation of an immune response, had baseline and Day 57 pseudoneutralisation data, and prior to Day 57 had no prohibited concomitant medications, Emergency Use Authorization (EUA) vaccinations, or positive polymerase chain reaction (PCR) test.

    Subject analysis set title
    Primary Vaccination Cohort:- AZD2816 (4) (Comparator)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Previously unvaccinated seronegative participants received IM AZD2816 5*10^10 vp on Days 1 and 29 (4-week dosing interval).

    Subject analysis set title
    Primary Vaccination Cohort:- AZD2816 (4) (Reference)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Previously unvaccinated seronegative participants received IM AZD2816 5*10^10 vp on Days 1 and 29 (4-week dosing interval).

    Subject analysis set title
    Primary Vaccination Cohort:- AZD1222+AZD2816 (4) (Comparator)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Previously unvaccinated seronegative participants received IM AZD1222 5*10^10 vp on Day 1 and IM AZD2816 5*10^10 vp on Day 29 (4-week dosing interval).

    Subject analysis set title
    Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) (Reference)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Previously unvaccinated seronegative participants received IM AZD1222 5*10^10 vp on Day 1 and IM AZD2816 5*10^10 vp on Day 29 (4-week dosing interval).

    Subject analysis set title
    Booster Cohort:- AZD1222:AZD2816 (Comparator)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Seronegative participants, who previously received 2 doses of AZD1222 vaccine according to the authorized dose and dosing regimen, with second dose administered at least 90 days prior to study treatment, received booster dose of IM AZD2816 5*10^10 vp on Day 1.

    Subject analysis set title
    Booster Cohort:- AZD1222:AZD2816 (Reference)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Seronegative participants, who previously received 2 doses of AZD1222 vaccine according to the authorized dose and dosing regimen, with second dose administered at least 90 days prior to study treatment, received booster dose of IM AZD2816 5*10^10 vp on Day 1.

    Subject analysis set title
    Booster Cohort:- AZD1222:AZD1222 (Comparator)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Seronegative participants, who previously received 2 doses of AZD1222 vaccine according to the authorized dose and dosing regimen, with second dose administered at least 90 days prior to study treatment, received booster dose of IM AZD1222 5*10^10 vp on Day 1.

    Subject analysis set title
    Booster Cohort:- AZD1222:AZD1222 (Reference)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Seronegative participants, who previously received 2 doses of AZD1222 vaccine according to the authorized dose and dosing regimen, with second dose administered at least 90 days prior to study treatment, received booster dose of IM AZD1222 5*10^10 vp on Day 1.

    Subject analysis set title
    Booster Cohort:- AZD1222:AZD2816 (Comparator)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Seronegative participants, who previously received 2 doses of AZD1222 vaccine according to the authorized dose and dosing regimen, with second dose administered at least 90 days prior to study treatment, received booster dose of IM AZD2816 5*10^10 vp on Day 1.

    Subject analysis set title
    Booster Cohort:- AZD1222:AZD2816 (Reference)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Seronegative participants, who previously received 2 doses of AZD1222 vaccine according to the authorized dose and dosing regimen, with second dose administered at least 90 days prior to study treatment, received booster dose of IM AZD2816 5*10^10 vp on Day 1.

    Subject analysis set title
    Booster Cohort:- mRNA:AZD2816 (Comparator)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Seronegative participants, who previously received 2 doses of approved mRNA based vaccine according to the authorized dose and dosing regimen, with second dose administered at least 90 days prior to study treatment, received booster dose of IM AZD2816 5*10^10 vp on Day 1.

    Subject analysis set title
    Booster Cohort:- mRNA:AZD2816 (Reference)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Seronegative participants, who previously received 2 doses of approved mRNA based vaccine according to the authorized dose and dosing regimen, with second dose administered at least 90 days prior to study treatment, received booster dose of IM AZD2816 5*10^10 vp on Day 1.

    Subject analysis set title
    Booster Cohort:- mRNA:AZD1222 (Comparator)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Seronegative participants, who previously received 2 doses of approved mRNA based vaccine according to the authorized dose and dosing regimen, with second dose administered at least 90 days prior to study treatment, received booster dose of IM AZD1222 5*10^10 vp on Day 1.

    Subject analysis set title
    Booster Cohort:- mRNA:AZD1222 (Reference)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Seronegative participants, who previously received 2 doses of approved mRNA based vaccine according to the authorized dose and dosing regimen, with second dose administered at least 90 days prior to study treatment, received booster dose of IM AZD1222 5*10^10 vp on Day 1.

    Subject analysis set title
    Booster Cohort:- mRNA:AZD2816 (Comparator)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Seronegative participants, who previously received 2 doses of approved mRNA based vaccine according to the authorized dose and dosing regimen, with second dose administered at least 90 days prior to study treatment, received booster dose of IM AZD2816 5*10^10 vp on Day 1.

    Subject analysis set title
    Booster Cohort:- mRNA:AZD2816 (Reference)
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Seronegative participants, who previously received 2 doses of approved mRNA based vaccine according to the authorized dose and dosing regimen, with second dose administered at least 90 days prior to study treatment, received booster dose of IM AZD2816 5*10^10 vp on Day 1.

    Primary: Number of Participants With Local and Systemic Solicited Treatment Emergent Adverse Events (TEAEs) in Primary Vaccination Cohort (PVC):- AZD2816 (4), Booster Cohorts:-AZD1222:AZD2816, and mRNA:AZD2816

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    End point title
    Number of Participants With Local and Systemic Solicited Treatment Emergent Adverse Events (TEAEs) in Primary Vaccination Cohort (PVC):- AZD2816 (4), Booster Cohorts:-AZD1222:AZD2816, and mRNA:AZD2816 [1] [2]
    End point description
    An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. Solicited AEs: local or systemic predefined events for assessment of reactogenicity. An e-diary was used to collect information on timing and severity of solicited AEs. Local AEs included pain, redness/erythema, tenderness, induration/swelling at site of injection. Systemic AEs included fever, chills, muscle pains, fatigue, headache, malaise, nausea, and vomiting. Seronegative safety analysis set: all participants who received at least 1 dose of study treatment, were analysed according to treatment actually received, and were seronegative at baseline. Here, number of subjects analyzed denotes those participants who were evaluated for solicited symptoms.
    End point type
    Primary
    End point timeframe
    During the 7-day follow-up period after vaccination (vaccines administered on Days 1 and 29 [only for primary vaccination cohort])
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Primary Vaccination Cohort:- AZD2816 (4) Booster Cohort:- AZD1222:AZD2816 Booster Cohort:- mRNA:AZD2816
    Number of subjects analysed
    375
    343
    299
    Units: Participants
        Any solicited AEs
    319
    275
    277
        Any local solicited AEs
    278
    225
    236
        Any systemic solicited AEs
    289
    211
    253
    No statistical analyses for this end point

    Primary: Number of Participants With Unsolicited TEAEs, Treatment-emergent Serious AEs (TESAEs), Medically Attended AEs (MAAEs), and Adverse Events of Special Interest (AESIs) in PVC:- AZD2816 (4), Booster Cohorts:- AZD1222:AZD2816, and mRNA:AZD2816

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    End point title
    Number of Participants With Unsolicited TEAEs, Treatment-emergent Serious AEs (TESAEs), Medically Attended AEs (MAAEs), and Adverse Events of Special Interest (AESIs) in PVC:- AZD2816 (4), Booster Cohorts:- AZD1222:AZD2816, and mRNA:AZD2816 [3] [4]
    End point description
    Unsolicited AEs (AEs other than solicited AEs) were collected by "open question" at study visits. TEAEs: AEs present at baseline that worsened in intensity after administration of study drug or AEs absent at baseline that emerged after administration of study drug. SAE: AE resulting in any of following outcomes/deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience; persistent or significant disability/incapacity; congenital anomaly. MAAE: AE leading to non-routine/unscheduled medically-attended visit, to or from medical doctor for any reason. AESI: AE of scientific/medical interest specific to further understanding of study drug safety profile and require close monitoring and rapid communication by investigators to Sponsor. Seronegative safety analysis set: all participants who received at least 1 dose of study treatment, were analysed according to treatment actually received, and were seronegative at baseline.
    End point type
    Primary
    End point timeframe
    During the 28-day follow-up period after vaccination (vaccines administered on Days 1 and 29 [only for primary vaccination cohort])
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Primary Vaccination Cohort:- AZD2816 (4) Booster Cohort:- AZD1222:AZD2816 Booster Cohort:- mRNA:AZD2816
    Number of subjects analysed
    379
    348
    302
    Units: Participants
        Any unsolicited TEAEs
    96
    70
    79
        Any TESAEs
    1
    0
    1
        Any MAAEs
    31
    26
    24
        Any AESIs
    10
    1
    6
    No statistical analyses for this end point

    Primary: Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Primary Vaccination Cohort:- AZD2816 (4), Booster Cohorts:-AZD1222:AZD2816 and mRNA:AZD2816

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    End point title
    Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Primary Vaccination Cohort:- AZD2816 (4), Booster Cohorts:-AZD1222:AZD2816 and mRNA:AZD2816 [5] [6]
    End point description
    Number of participants with abnormal laboratory parameters reported as TEAEs are reported. Laboratory tests included haematology and clinical chemistry. Seronegative safety analysis set included all participants who received at least 1 dose of study treatment, were analysed according to treatment actually received, and were seronegative at baseline.
    End point type
    Primary
    End point timeframe
    During the 28-day follow-up period after vaccination (vaccines administered on Days 1 and 29 [only for primary vaccination cohort])
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Primary Vaccination Cohort:- AZD2816 (4) Booster Cohort:- AZD1222:AZD2816 Booster Cohort:- mRNA:AZD2816
    Number of subjects analysed
    379
    348
    302
    Units: Participants
        Anaemia
    1
    0
    0
        Eosinophilia
    1
    0
    1
        Iron deficiency anaemia
    2
    0
    1
        Hypercholesterolaemia
    1
    0
    0
        Alanine aminotransferase increased
    1
    0
    0
        Fibrin D dimer increased
    1
    2
    4
        Haematocrit decreased
    1
    0
    0
        Haemoglobin decreased
    2
    0
    0
        Transaminases increased
    1
    0
    0
        Lymphopenia
    0
    1
    0
        Normochromic normocytic anaemia
    0
    1
    0
        Thrombocytopenia
    0
    1
    0
        Hyponatraemia
    0
    1
    0
        Blood creatine increased
    0
    1
    0
        White blood cell count increased
    0
    2
    0
        Aspartate aminotransferase increased
    0
    0
    1
        Blood alkaline phosphatase increased
    0
    0
    1
        Blood fibrinogen increased
    0
    0
    2
        Vitamin D decreased
    0
    0
    1
    No statistical analyses for this end point

    Primary: Geometric Mean Titre (GMT) of SARS-CoV-2 Neutralizing Antibodies (nAb) Against B.1.351 Variant Elicited by Primary Vaccination Cohort:- AZD2816 (4) and the Original Wuhan-Hu-1 Strain Elicited by Primary Vaccination Cohort:- AZD1222 (4)

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    End point title
    Geometric Mean Titre (GMT) of SARS-CoV-2 Neutralizing Antibodies (nAb) Against B.1.351 Variant Elicited by Primary Vaccination Cohort:- AZD2816 (4) and the Original Wuhan-Hu-1 Strain Elicited by Primary Vaccination Cohort:- AZD1222 (4) [7]
    End point description
    Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) nAb were measured by pseudoneutralisation assay. GMT was calculated as antilogarithm of Σ(log base 2 transformed titre/n), i.e. as anti-logarithm transformation of the mean of log-transformed titre, where 'n' was the number of participants with titre information. PVC:- AZD2816 (4) with response against B.1.351 variant is comparator group and PVC:- AZD1222 (4) with response against the original Wuhan-Hu-1 strain is reference group. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Primary
    End point timeframe
    28 days after second dose (Day 57)
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Primary Vaccination Cohort:- AZD1222 (4) Primary Vaccination Cohort:- AZD2816 (4)
    Number of subjects analysed
    348
    342
    Units: 1/dilution
        geometric mean (confidence interval 95%)
    661.29 (617.16 to 708.57)
    790.96 (735.29 to 850.85)
    Statistical analysis title
    GMT Ratio
    Statistical analysis description
    The analyses were derived using analysis of covariance (ANCOVA).
    Comparison groups
    Primary Vaccination Cohort:- AZD2816 (4) v Primary Vaccination Cohort:- AZD1222 (4)
    Number of subjects included in analysis
    690
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [8]
    Method
    Parameter type
    GMT ratio
    Point estimate
    1.19
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.08
         upper limit
    1.32
    Notes
    [8] - Noninferiority was demonstrated if the lower limit of the 2-sided 95% confidence interval (CI) of the GMT ratio of the comparator group and reference group was > 0.67.

    Primary: GMT of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Booster Cohort:- AZD1222:AZD1222 and AZD1222 in Historical Control

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    End point title
    GMT of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Booster Cohort:- AZD1222:AZD1222 and AZD1222 in Historical Control [9]
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. GMT was calculated as antilogarithm of Σ(log base 2 transformed titre/n), i.e. as anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Booster Cohort:- AZD1222:AZD1222 is the comparator group and AZD1222 in Historical Control is the reference group, both compared for response against the original Wuhan-Hu-1 strain. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Primary
    End point timeframe
    Booster Cohort: 28 days after booster dose (Day 29) and Historical Control: 28 days after the second dose (Day 57)
    Notes
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Booster Cohort:- AZD1222:AZD1222 Historical Control
    Number of subjects analysed
    329
    508
    Units: 1/dilution
        geometric mean (confidence interval 95%)
    246.45 (227.39 to 267.12)
    242.80 (224.82 to 262.23)
    Statistical analysis title
    GMT Ratio
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Booster Cohort:- AZD1222:AZD1222 v Historical Control
    Number of subjects included in analysis
    837
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [10]
    Method
    Parameter type
    GMT ratio
    Point estimate
    1.02
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.9
         upper limit
    1.14
    Notes
    [10] - Noninferiority was demonstrated if the lower limit of the 2-sided 95% CI of the GMT ratio of the comparator group and reference group is > 0.67.

    Primary: Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against the B.1.351 Variant Elicited by Primary Vaccination Cohort:- AZD2816 (4) and the Original Wuhan-Hu-1 Strain Elicited by Primary Vaccination Cohort:- AZD1222 (4)

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    End point title
    Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against the B.1.351 Variant Elicited by Primary Vaccination Cohort:- AZD2816 (4) and the Original Wuhan-Hu-1 Strain Elicited by Primary Vaccination Cohort:- AZD1222 (4) [11]
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as >= 4-fold increase in the GMT of nAb from baseline. Primary Vaccination Cohort:- AZD2816 (4) with response against B.1.351 variant is the comparator group and Primary Vaccination Cohort:- AZD1222 (4) with response against the original Wuhan-Hu-1 strain is the reference group. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Primary
    End point timeframe
    28 days after second dose (Day 57)
    Notes
    [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Primary Vaccination Cohort:- AZD1222 (4) Primary Vaccination Cohort:- AZD2816 (4)
    Number of subjects analysed
    344
    342
    Units: Percentage of participants
        number (confidence interval 95%)
    87.79 (83.86 to 91.06)
    89.47 (85.73 to 92.52)
    Statistical analysis title
    Seroresponse difference
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Primary Vaccination Cohort:- AZD2816 (4) v Primary Vaccination Cohort:- AZD1222 (4)
    Number of subjects included in analysis
    686
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [12]
    Method
    Parameter type
    Seroresponse difference
    Point estimate
    1.68
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.11
         upper limit
    6.49
    Notes
    [12] - Non-inferiority was demonstrated if the lower limit of the 2-sided 95% CI rate difference in seroresponse between the comparator group and reference group was > or =-10%.

    Primary: GMT of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Booster Cohort:- mRNA:AZD1222 and AZD1222 in Historical Control

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    End point title
    GMT of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Booster Cohort:- mRNA:AZD1222 and AZD1222 in Historical Control [13]
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. GMT was calculated as antilogarithm of Σ(log base 2 transformed titre/n), i.e. as anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Booster Cohort:- mRNA:AZD1222 is the comparator group and AZD1222 in Historical Control is the reference group, both compared for response against the original Wuhan-Hu-1 strain. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Primary
    End point timeframe
    Booster Cohort: 28 days after booster dose (Day 29) and Historical Control: 28 days after the second dose (Day 57)
    Notes
    [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Booster Cohort:- mRNA:AZD1222 Historical Control
    Number of subjects analysed
    280
    508
    Units: 1/dilution
        geometric mean (confidence interval 95%)
    841.96 (790.34 to 896.96)
    242.80 (224.82 to 262.23)
    Statistical analysis title
    GMT Ratio
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Booster Cohort:- mRNA:AZD1222 v Historical Control
    Number of subjects included in analysis
    788
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [14]
    Method
    Parameter type
    GMT ratio
    Point estimate
    3.47
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    3.09
         upper limit
    3.89
    Notes
    [14] - Noninferiority was demonstrated if the lower limit of the 2-sided 95% CI of the GMT ratio of the comparator group and reference group is > 0.67.

    Secondary: Number of Participants With Local and Systemic Solicited TEAEs

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    End point title
    Number of Participants With Local and Systemic Solicited TEAEs [15]
    End point description
    AE: any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. TEAEs: AEs present at baseline that worsened in intensity after administration of study drug or AEs absent at baseline that emerged after administration of study drug. Solicited AEs are local or systemic predefined events for assessment of reactogenicity. An e-diary was used to collect information on timing and severity of solicited AEs. Local AEs included pain, redness/erythema, tenderness, induration/swelling at the site of the injection. Systemic AEs included fever (>100°F/37.8°C), chills, muscle pains, fatigue, headache, malaise, nausea, and vomiting. Seronegative safety analysis set included all participants who received at least 1 dose of study treatment, were analysed according to treatment actually received, and were seronegative at baseline. Here, number of subjects analyzed denotes those participants who were evaluated for solicited symptoms.
    End point type
    Secondary
    End point timeframe
    During the 7-day follow-up period after vaccination (vaccines administered on Days 1 and 29 or Day 85 [only for primary vaccination cohorts])
    Notes
    [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) Primary Vaccination Cohort:- AZD2816 (12) Booster Cohort:- AZD1222:AZD1222 Booster Cohort:- mRNA:AZD1222
    Number of subjects analysed
    373
    188
    340
    299
    Units: Participants
        Any solicited AEs
    322
    168
    266
    269
        Any local solicited AEs
    285
    146
    209
    228
        Any systemic solicited AEs
    296
    153
    206
    238
    No statistical analyses for this end point

    Secondary: Number of Participants With Unsolicited TEAEs, TESAEs, MAAEs, and AESIs

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    End point title
    Number of Participants With Unsolicited TEAEs, TESAEs, MAAEs, and AESIs [16]
    End point description
    Unsolicited AEs (AEs other than solicited AEs) were collected by "open question" at study visits. TEAEs: AEs present at baseline that worsened in intensity after administration of study drug or AEs absent at baseline that emerged after administration of study drug. SAE: AE resulting in any of following outcomes/deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience; persistent or significant disability/incapacity; congenital anomaly. MAAE: AE leading to non-routine/unscheduled medically-attended visit, to or from medical doctor for any reason. AESI: AE of scientific/medical interest specific to further understanding of study drug safety profile and require close monitoring and rapid communication by investigators to Sponsor. Seronegative safety analysis set: all participants who received at least 1 dose of study treatment, were analysed according to treatment actually received, and were seronegative at baseline.
    End point type
    Secondary
    End point timeframe
    During the 28-day follow-up period after vaccination (vaccines administered on Days 1 and 29 or Day 85 [only for primary vaccination cohorts])
    Notes
    [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) Primary Vaccination Cohort:- AZD2816 (12) Booster Cohort:- AZD1222:AZD1222 Booster Cohort:- mRNA:AZD1222
    Number of subjects analysed
    380
    191
    349
    300
    Units: Participants
        Any unsolicited TEAEs
    93
    67
    81
    73
        Any TESAEs
    2
    0
    0
    0
        Any MAAEs
    37
    25
    34
    16
        Any AESIs
    9
    7
    3
    6
    No statistical analyses for this end point

    Secondary: GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Primary Vaccination Cohort:- AZD2816 (4) and Primary Vaccination Cohort:- AZD1222 (4)

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    End point title
    GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Primary Vaccination Cohort:- AZD2816 (4) and Primary Vaccination Cohort:- AZD1222 (4) [17]
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. GMT was calculated as antilogarithm of Σ(log base 2 transformed titre/n), i.e. as anti-logarithm transformation of the mean of log-transformed titre, where 'n' was the number of participants with titre information. Primary Vaccination Cohort:- AZD2816 (4) is the comparator group and Primary Vaccination Cohort:- AZD1222 (4) is the reference group, both compared for response against B.1.351 variant. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    28 days after second dose (Day 57)
    Notes
    [17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Primary Vaccination Cohort:- AZD1222 (4) Primary Vaccination Cohort:- AZD2816 (4)
    Number of subjects analysed
    348
    342
    Units: 1/dilution
        geometric mean (confidence interval 95%)
    269.89 (260.72 to 279.37)
    865.48 (837.85 to 894.02)
    Statistical analysis title
    GMT Ratio
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Primary Vaccination Cohort:- AZD2816 (4) v Primary Vaccination Cohort:- AZD1222 (4)
    Number of subjects included in analysis
    690
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [18]
    Method
    Parameter type
    GMT ratio
    Point estimate
    3.21
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    3.06
         upper limit
    3.36
    Notes
    [18] - Noninferiority was demonstrated if the lower limit of the 2-sided 95% CI of the GMT ratio of the comparator group and reference group was > 0.67.

    Secondary: GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) and the Original Wuhan-Hu-1 Strain Elicited by Primary Vaccination Cohort:- AZD1222 (4)

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    End point title
    GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) and the Original Wuhan-Hu-1 Strain Elicited by Primary Vaccination Cohort:- AZD1222 (4) [19]
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. GMT was calculated as antilogarithm of Σ(log base 2 transformed titre/n), i.e. as anti-logarithm transformation of the mean of log-transformed titre, where 'n' was the number of participants with titre information. PVC:- AZD1222 + AZD2816 (4) with response against B.1.351 variant is the comparator group and PVC:- AZD1222 (4) with response against the original Wuhan-Hu-1 strain is the reference group. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    28 days after second dose (Day 57)
    Notes
    [19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Primary Vaccination Cohort:- AZD1222 (4) Primary Vaccination Cohort:- AZD1222 + AZD2816 (4)
    Number of subjects analysed
    348
    334
    Units: 1/dilution
        geometric mean (confidence interval 95%)
    800.92 (745.59 to 860.36)
    405.20 (373.64 to 439.43)
    Statistical analysis title
    GMT Ratio
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) v Primary Vaccination Cohort:- AZD1222 (4)
    Number of subjects included in analysis
    682
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [20]
    Method
    Parameter type
    GMT ratio
    Point estimate
    0.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.45
         upper limit
    0.56
    Notes
    [20] - Noninferiority was demonstrated if the lower limit of the 2-sided 95% CI of the GMT ratio of the comparator group and reference group was > 0.67.

    Secondary: GMT of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Primary Vaccination Cohort:- AZD2816 (4) and Primary Vaccination Cohort:- AZD1222 (4)

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    End point title
    GMT of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Primary Vaccination Cohort:- AZD2816 (4) and Primary Vaccination Cohort:- AZD1222 (4) [21]
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. GMT was calculated as antilogarithm of Σ(log base 2 transformed titre/n), i.e. as anti-logarithm transformation of the mean of log-transformed titre, where 'n' was the number of participants with titre information. Primary Vaccination Cohort:-AZD2816 (4) is comparator group and Primary Vaccination Cohort:- AZD1222 (4) is reference group, both compared for response against the original Wuhan-Hu-1 strain. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre,and no protocol deviations judged to have potential to interfere with antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    28 days after second dose (Day 57)
    Notes
    [21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Primary Vaccination Cohort:- AZD1222 (4) Primary Vaccination Cohort:- AZD2816 (4)
    Number of subjects analysed
    348
    342
    Units: 1/dilution
        geometric mean (confidence interval 95%)
    719.37 (654.68 to 790.46)
    222.75 (201.60 to 246.12)
    Statistical analysis title
    GMT Ratio
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Primary Vaccination Cohort:- AZD2816 (4) v Primary Vaccination Cohort:- AZD1222 (4)
    Number of subjects included in analysis
    690
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [22]
    Method
    Parameter type
    GMT ratio
    Point estimate
    0.31
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.27
         upper limit
    0.35
    Notes
    [22] - Noninferiority was demonstrated if the lower limit of the 2-sided 95% CI of the GMT ratio of the comparator group and reference group was > 0.67.

    Secondary: GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- AZD1222:AZD2816 and the Original Wuhan-Hu-1 Strain Elicited by AZD1222 in Historical Control

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    End point title
    GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- AZD1222:AZD2816 and the Original Wuhan-Hu-1 Strain Elicited by AZD1222 in Historical Control [23]
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. GMT was calculated as antilogarithm of Σ(log base 2 transformed titre/n), i.e. as anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Booster Cohort:- AZD1222:AZD2816 with response against B.1.351 variant is the comparator group and AZD1222 in Historical Control with response against the original Wuhan-Hu-1 strain is the reference group. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    Booster Cohort: 28 days after booster dose (Day 29) and Historical Control: 28 days after the second dose (Day 57)
    Notes
    [23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Booster Cohort:- AZD1222:AZD2816 Historical Control
    Number of subjects analysed
    322
    508
    Units: 1/dilution
        geometric mean (confidence interval 95%)
    341.96 (315.48 to 370.66)
    242.80 (224.82 to 262.23)
    Statistical analysis title
    GMT Ratio
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Booster Cohort:- AZD1222:AZD2816 v Historical Control
    Number of subjects included in analysis
    830
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [24]
    Method
    Parameter type
    GMT ratio
    Point estimate
    1.41
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.25
         upper limit
    1.58
    Notes
    [24] - Noninferiority was demonstrated if the lower limit of the 2-sided 95% CI of the GMT ratio of the comparator group and reference group was > 0.67.

    Secondary: GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- AZD1222:AZD2816 and Booster Cohort:- AZD1222:AZD1222

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    End point title
    GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- AZD1222:AZD2816 and Booster Cohort:- AZD1222:AZD1222 [25]
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Booster Cohort:- AZD1222:AZD2816 is the comparator group and Booster Cohort:- AZD1222:AZD1222 is the reference group, both compared for response against B.1.351 variant. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    28 days after booster dose (Day 29)
    Notes
    [25] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Booster Cohort:- AZD1222:AZD1222 Booster Cohort:- AZD1222:AZD2816
    Number of subjects analysed
    329
    322
    Units: 1/dilution
        geometric mean (confidence interval 95%)
    185.70 (169.32 to 203.66)
    341.96 (315.48 to 370.66)
    Statistical analysis title
    GMT Ratio
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Booster Cohort:- AZD1222:AZD2816 v Booster Cohort:- AZD1222:AZD1222
    Number of subjects included in analysis
    651
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [26]
    Method
    Parameter type
    GMT ratio
    Point estimate
    1.84
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.63
         upper limit
    2.08
    Notes
    [26] - Noninferiority was demonstrated if the lower limit of the 2-sided 95% CI of the GMT ratio of the comparator group and reference group was > 0.67.

    Secondary: GMT of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Booster Cohort:- AZD1222:AZD2816 and AZD1222 in Historical Control

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    End point title
    GMT of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Booster Cohort:- AZD1222:AZD2816 and AZD1222 in Historical Control [27]
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Booster Cohort:- AZD1222:AZD2816 is the comparator group and AZD1222 in Historical Control is the reference group, both compared for response against the original Wuhan-Hu-1 strain. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    Booster Cohort: 28 days after booster dose (Day 29) and Historical Control: 28 days after the second dose (Day 57)
    Notes
    [27] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Booster Cohort:- AZD1222:AZD2816 Historical Control
    Number of subjects analysed
    322
    508
    Units: 1/dilution
        geometric mean (confidence interval 95%)
    213.26 (197.45 to 230.34)
    242.80 (224.82 to 262.23)
    Statistical analysis title
    GMT Ratio
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Booster Cohort:- AZD1222:AZD2816 v Historical Control
    Number of subjects included in analysis
    830
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [28]
    Method
    Parameter type
    GMT ratio
    Point estimate
    0.88
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.78
         upper limit
    0.99
    Notes
    [28] - Noninferiority was demonstrated if the lower limit of the 2-sided 95% CI of the GMT ratio of the comparator group and reference group was > 0.67.

    Secondary: GMT of SARS-CoV-2 nAb Against the original Wuhan-Hu-1 Strain Elicited by Booster Cohort:- AZD1222:AZD2816 and Booster Cohort:- AZD1222:AZD1222

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    End point title
    GMT of SARS-CoV-2 nAb Against the original Wuhan-Hu-1 Strain Elicited by Booster Cohort:- AZD1222:AZD2816 and Booster Cohort:- AZD1222:AZD1222 [29]
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Booster Cohort:- AZD1222:AZD2816 is the comparator group and Booster Cohort:- AZD1222:AZD1222 is the reference group, both compared for response against the original Wuhan-Hu-1 strain. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    28 days after booster dose (Day 29)
    Notes
    [29] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Booster Cohort:- AZD1222:AZD1222 Booster Cohort:- AZD1222:AZD2816
    Number of subjects analysed
    329
    322
    Units: 1/dilution
        geometric mean (confidence interval 95%)
    246.45 (227.39 to 267.12)
    213.26 (197.45 to 230.34)
    Statistical analysis title
    GMT Ratio
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Booster Cohort:- AZD1222:AZD2816 v Booster Cohort:- AZD1222:AZD1222
    Number of subjects included in analysis
    651
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [30]
    Method
    Parameter type
    GMT ratio
    Point estimate
    0.87
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.78
         upper limit
    0.97
    Notes
    [30] - Noninferiority was demonstrated if the lower limit of the 2-sided 95% CI of the GMT ratio of the comparator group and reference group was > 0.67.

    Secondary: GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- AZD1222:AZD2816 and Primary Vaccination Cohort:- AZD1222 (4)

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    End point title
    GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- AZD1222:AZD2816 and Primary Vaccination Cohort:- AZD1222 (4) [31]
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Booster Cohort:- AZD1222:AZD2816 is the comparator group and Primary Vaccination Cohort:- AZD1222 (4) is the reference group, both compared for response against B.1.351 variant. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    Booster Cohort: 28 days after booster dose (Day 29) and Primary Vaccination Cohort: 28 days after the second dose (Day 57)
    Notes
    [31] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Primary Vaccination Cohort:- AZD1222 (4) Booster Cohort:- AZD1222:AZD2816
    Number of subjects analysed
    348
    322
    Units: 1/dilution
        geometric mean (confidence interval 95%)
    360.43 (324.90 to 399.84)
    341.96 (315.48 to 370.66)
    Statistical analysis title
    GMT Ratio
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Booster Cohort:- AZD1222:AZD2816 v Primary Vaccination Cohort:- AZD1222 (4)
    Number of subjects included in analysis
    670
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [32]
    Method
    Parameter type
    GMT ratio
    Point estimate
    0.95
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.83
         upper limit
    1.08
    Notes
    [32] - Noninferiority was demonstrated if the lower limit of the 2-sided 95% CI of the GMT ratio of the comparator group and reference group was > 0.67.

    Secondary: GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- mRNA:AZD2816 and Booster Cohort:- mRNA:AZD1222

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    End point title
    GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- mRNA:AZD2816 and Booster Cohort:- mRNA:AZD1222 [33]
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Booster Cohort:- mRNA:AZD2816 is the comparator group and Booster Cohort:- mRNA:AZD1222 is the reference group, both compared for response against B.1.351 variant. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    28 days after booster dose (Day 29)
    Notes
    [33] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Booster Cohort:- mRNA:AZD1222 Booster Cohort:- mRNA:AZD2816
    Number of subjects analysed
    280
    280
    Units: 1/dilution
        geometric mean (confidence interval 95%)
    718.90 (670.46 to 770.84)
    1587.58 (1463.98 to 1721.61)
    Statistical analysis title
    GMT Ratio
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Booster Cohort:- mRNA:AZD2816 v Booster Cohort:- mRNA:AZD1222
    Number of subjects included in analysis
    560
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [34]
    Method
    Parameter type
    GMT ratio
    Point estimate
    2.22
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.99
         upper limit
    2.47
    Notes
    [34] - Noninferiority was demonstrated if the lower limit of the 2-sided 95% CI of the GMT ratio of the comparator group and reference group was > 0.67.

    Secondary: GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- mRNA:AZD2816 and the Original Wuhan-Hu-1 Strain Elicited by AZD1222 in Historical Control

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    End point title
    GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- mRNA:AZD2816 and the Original Wuhan-Hu-1 Strain Elicited by AZD1222 in Historical Control [35]
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Booster Cohort:- mRNA:AZD2816 with response against B.1.351 variant is the comparator group and AZD1222 in Historical Control with response against the original Wuhan-Hu-1 strain is the reference group. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    Booster Cohort: 28 days after booster dose (Day 29) and Historical Control: 28 days after the second dose (Day 57)
    Notes
    [35] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Booster Cohort:- mRNA:AZD2816 Historical Control
    Number of subjects analysed
    280
    508
    Units: 1/dilution
        geometric mean (confidence interval 95%)
    1587.58 (1463.98 to 1721.61)
    242.80 (224.82 to 262.23)
    Statistical analysis title
    GMT Ratio
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Booster Cohort:- mRNA:AZD2816 v Historical Control
    Number of subjects included in analysis
    788
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [36]
    Method
    Parameter type
    GMT ratio
    Point estimate
    6.56
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    5.82
         upper limit
    7.4
    Notes
    [36] - Noninferiority was demonstrated if the lower limit of the 2-sided 95% CI of the GMT ratio of the comparator group and reference group was > 0.67.

    Secondary: GMT of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Booster Cohort:- mRNA:AZD2816 and AZD1222 in Historical Control

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    End point title
    GMT of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Booster Cohort:- mRNA:AZD2816 and AZD1222 in Historical Control [37]
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Booster Cohort:- mRNA:AZD2816 is the comparator group and AZD1222 in Historical Control is the reference group, both compared for response against the original Wuhan-Hu-1 strain. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    Booster Cohort: 28 days after booster dose (Day 29) and Historical Control: 28 days after the second dose (Day 57)
    Notes
    [37] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Booster Cohort:- mRNA:AZD2816 Historical Control
    Number of subjects analysed
    280
    508
    Units: 1/dilution
        geometric mean (confidence interval 95%)
    1052.73 (974.55 to 1137.19)
    242.80 (224.82 to 262.23)
    Statistical analysis title
    GMT Ratio
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Booster Cohort:- mRNA:AZD2816 v Historical Control
    Number of subjects included in analysis
    788
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [38]
    Method
    Parameter type
    GMT ratio
    Point estimate
    4.35
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    3.86
         upper limit
    4.9
    Notes
    [38] - Noninferiority was demonstrated if the lower limit of the 2-sided 95% CI of the GMT ratio of the comparator group and reference group is > 0.67.

    Secondary: GMT of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Booster Cohort:- mRNA:AZD2816 and Booster Cohort:- mRNA:AZD1222

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    End point title
    GMT of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Booster Cohort:- mRNA:AZD2816 and Booster Cohort:- mRNA:AZD1222 [39]
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Booster Cohort:- mRNA:AZD2816 is the comparator group and Booster Cohort:- mRNA:AZD1222 is the reference group, both compared for response against the original Wuhan-Hu-1 strain. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    28 days after booster dose (Day 29)
    Notes
    [39] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Booster Cohort:- mRNA:AZD1222 Booster Cohort:- mRNA:AZD2816
    Number of subjects analysed
    280
    280
    Units: 1/dilution
        geometric mean (confidence interval 95%)
    841.96 (790.34 to 896.96)
    1052.73 (974.55 to 1137.19)
    Statistical analysis title
    GMT Ratio
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Booster Cohort:- mRNA:AZD2816 v Booster Cohort:- mRNA:AZD1222
    Number of subjects included in analysis
    560
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [40]
    Method
    Parameter type
    GMT ratio
    Point estimate
    1.25
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.13
         upper limit
    1.39
    Notes
    [40] - Noninferiority was demonstrated if the lower limit of the 2-sided 95% CI of the GMT ratio of the comparator group and reference group was > 0.67.

    Secondary: GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- mRNA:AZD2816 and Primary Vaccination Cohort:- AZD1222 (4)

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    End point title
    GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- mRNA:AZD2816 and Primary Vaccination Cohort:- AZD1222 (4) [41]
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Booster Cohort:- mRNA:AZD2816 is the comparator group and Primary Vaccination Cohort:- AZD1222 (4) is the reference group, both compared for response against B.1.351 variant. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    Booster Cohort: 28 days after booster dose (Day 29) and Primary Vaccination Cohort: 28 days after the second dose (Day 57)
    Notes
    [41] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Primary Vaccination Cohort:- AZD1222 (4) Booster Cohort:- mRNA:AZD2816
    Number of subjects analysed
    348
    280
    Units: 1/dilution
        geometric mean (confidence interval 95%)
    360.43 (324.90 to 399.84)
    1587.58 (1463.98 to 1721.61)
    Statistical analysis title
    GMT Ratio
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Booster Cohort:- mRNA:AZD2816 v Primary Vaccination Cohort:- AZD1222 (4)
    Number of subjects included in analysis
    628
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [42]
    Method
    Parameter type
    GMT ratio
    Point estimate
    4.42
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    3.85
         upper limit
    5.08
    Notes
    [42] - Noninferiority was demonstrated if the lower limit of the 2-sided 95% CI of the GMT ratio of the comparator group and reference group was > 0.67.

    Secondary: Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- AZD1222:AZD2816 and the Original Wuhan-Hu-1 Strain Elicited by AZD1222 in Historical Control

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    End point title
    Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- AZD1222:AZD2816 and the Original Wuhan-Hu-1 Strain Elicited by AZD1222 in Historical Control [43]
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as >= 4-fold increase in the GMT of nAb from baseline. Booster Cohort:- AZD1222:AZD2816 with response against B.1.351 variant is the comparator group and AZD1222 in Historical Control with response against the original Wuhan-Hu-1 strain is the reference group. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    Booster Cohort: 28 days after booster dose (Day 29) and Historical Control: 28 days after the second dose (Day 57)
    Notes
    [43] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Booster Cohort:- AZD1222:AZD2816 Historical Control
    Number of subjects analysed
    320
    508
    Units: Percentage of participants
        number (confidence interval 95%)
    82.81 (78.22 to 86.78)
    84.06 (80.58 to 87.13)
    Statistical analysis title
    Seroresponse Difference
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Booster Cohort:- AZD1222:AZD2816 v Historical Control
    Number of subjects included in analysis
    828
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [44]
    Method
    Parameter type
    Seroresponse difference
    Point estimate
    -1.24
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -6.62
         upper limit
    3.84
    Notes
    [44] - Non-inferiority was demonstrated if the lower limit of the 2-sided 95% CI rate difference in seroresponse between the comparator group and reference group was > or =-10%.

    Secondary: Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- AZD1222:AZD2816 and Booster Cohort:- AZD1222:AZD1222

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    End point title
    Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- AZD1222:AZD2816 and Booster Cohort:- AZD1222:AZD1222 [45]
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as >= 4-fold increase in the GMT of nAb from baseline. Booster Cohort:- AZD1222:AZD2816 is the comparator group and Booster Cohort:- AZD1222:AZD1222 is the reference group, both compared for response against B.1.351 variant. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    28 days after booster dose (Day 29)
    Notes
    [45] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Booster Cohort:- AZD1222:AZD1222 Booster Cohort:- AZD1222:AZD2816
    Number of subjects analysed
    329
    320
    Units: Percentage of participants
        number (confidence interval 95%)
    65.96 (60.56 to 71.07)
    82.81 (78.22 to 86.78)
    Statistical analysis title
    Seroresponse Difference
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Booster Cohort:- AZD1222:AZD2816 v Booster Cohort:- AZD1222:AZD1222
    Number of subjects included in analysis
    649
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [46]
    Method
    Parameter type
    Seroresponse difference
    Point estimate
    16.86
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    10.18
         upper limit
    23.32
    Notes
    [46] - Non-inferiority was demonstrated if the lower limit of the 2-sided 95% CI rate difference in seroresponse between the comparator group and reference group was > or =-10%.

    Secondary: Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Booster Cohort:- AZD1222:AZD2816 and AZD1222 in Historical Control

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    End point title
    Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Booster Cohort:- AZD1222:AZD2816 and AZD1222 in Historical Control [47]
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as >= 4-fold increase in the GMT of nAb from baseline. Booster Cohort:- AZD1222:AZD2816 is the comparator group and AZD1222 in Historical Control is the reference group, both compared for response against the original Wuhan-Hu-1 strain. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    Booster Cohort: 28 days after booster dose (Day 29) and Historical Control: 28 days after the second dose (Day 57)
    Notes
    [47] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Booster Cohort:- AZD1222:AZD2816 Historical Control
    Number of subjects analysed
    320
    508
    Units: Percentage of participants
        number (confidence interval 95%)
    65.94 (60.46 to 71.12)
    84.06 (80.58 to 87.13)
    Statistical analysis title
    Seroresponse Difference
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Booster Cohort:- AZD1222:AZD2816 v Historical Control
    Number of subjects included in analysis
    828
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [48]
    Method
    Parameter type
    Seroresponse difference
    Point estimate
    -18.12
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -24.22
         upper limit
    -12.07
    Notes
    [48] - Non-inferiority was demonstrated if the lower limit of the 2-sided 95% CI rate difference in seroresponse between the comparator group and reference group was > or =-10%.

    Secondary: Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Booster Cohort:- AZD1222:AZD2816 and Booster Cohort:- AZD1222:AZD1222

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    End point title
    Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Booster Cohort:- AZD1222:AZD2816 and Booster Cohort:- AZD1222:AZD1222 [49]
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as >= 4-fold increase in the GMT of nAb from baseline. Booster Cohort:- AZD1222:AZD2816 is the comparator group and Booster Cohort:- AZD1222:AZD1222 is the reference group, both compared for response against the original Wuhan-Hu-1 strain. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    28 days after booster dose (Day 29)
    Notes
    [49] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Booster Cohort:- AZD1222:AZD1222 Booster Cohort:- AZD1222:AZD2816
    Number of subjects analysed
    329
    320
    Units: Percentage of participants
        number (confidence interval 95%)
    65.96 (60.56 to 71.07)
    65.94 (60.46 to 71.12)
    Statistical analysis title
    Seroresponse Difference
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Booster Cohort:- AZD1222:AZD2816 v Booster Cohort:- AZD1222:AZD1222
    Number of subjects included in analysis
    649
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [50]
    Method
    Parameter type
    Seroresponse difference
    Point estimate
    -0.02
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -7.28
         upper limit
    7.23
    Notes
    [50] - Non-inferiority was demonstrated if the lower limit of the 2-sided 95% CI rate difference in seroresponse between the comparator group and reference group was > or =-10%.

    Secondary: Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- mRNA:AZD2816 and the Original Wuhan-Hu-1 Strain Elicited by AZD1222 in Historical Control

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    End point title
    Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- mRNA:AZD2816 and the Original Wuhan-Hu-1 Strain Elicited by AZD1222 in Historical Control [51]
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as >= 4-fold increase in the GMT of nAb from baseline. Booster Cohort:- mRNA:AZD2816 with response against B.1.351 variant is the comparator group and AZD1222 in Historical Control with response against the original Wuhan-Hu-1 strain is the reference group. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    Booster Cohort: 28 days after booster dose (Day 29) and Historical Control: 28 days after the second dose (Day 57)
    Notes
    [51] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Booster Cohort:- mRNA:AZD2816 Historical Control
    Number of subjects analysed
    277
    508
    Units: Percentage of participants
        number (confidence interval 95%)
    80.51 (75.34 to 85.00)
    84.06 (80.58 to 87.13)
    Statistical analysis title
    Seroresponse Difference
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Booster Cohort:- mRNA:AZD2816 v Historical Control
    Number of subjects included in analysis
    785
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [52]
    Method
    Parameter type
    Seroresponse difference
    Point estimate
    -3.55
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -9.4
         upper limit
    1.9
    Notes
    [52] - Non-inferiority was demonstrated if the lower limit of the 2-sided 95% CI rate difference in seroresponse between the comparator group and reference group was > or =-10%.

    Secondary: Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- AZD1222:AZD2816 and Primary Vaccination Cohort:- AZD1222 (4)

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    End point title
    Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- AZD1222:AZD2816 and Primary Vaccination Cohort:- AZD1222 (4) [53]
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as >= 4-fold increase in the GMT of nAb from baseline. Booster Cohort:- AZD1222:AZD2816 is the comparator group and Primary Vaccination Cohort:- AZD1222 (4) is the reference group, both compared for response against B.1.351 variant. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    Booster Cohort: 28 days after booster dose (Day 29) and Primary Vaccination Cohort: 28 days after the second dose (Day 57)
    Notes
    [53] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Primary Vaccination Cohort:- AZD1222 (4) Booster Cohort:- AZD1222:AZD2816
    Number of subjects analysed
    344
    320
    Units: Percentage of participants
        number (confidence interval 95%)
    51.45 (46.03 to 56.85)
    82.81 (78.22 to 86.78)
    Statistical analysis title
    Seroresponse Difference
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Booster Cohort:- AZD1222:AZD2816 v Primary Vaccination Cohort:- AZD1222 (4)
    Number of subjects included in analysis
    664
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [54]
    Method
    Parameter type
    Seroresponse difference
    Point estimate
    31.36
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    24.44
         upper limit
    37.82
    Notes
    [54] - Non-inferiority was demonstrated if the lower limit of the 2-sided 95% CI rate difference in seroresponse between the comparator group and reference group was > or =-10%.

    Secondary: Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- mRNA:AZD2816 and Booster Cohort:- mRNA:AZD1222

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    End point title
    Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- mRNA:AZD2816 and Booster Cohort:- mRNA:AZD1222 [55]
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as >= 4-fold increase in the GMT of nAb from baseline. Booster Cohort:- mRNA:AZD2816 is the comparator group and Booster Cohort:- mRNA:AZD1222 is the reference group, both compared for response against B.1.351 variant. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    28 days after booster dose (Day 29)
    Notes
    [55] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Booster Cohort:- mRNA:AZD1222 Booster Cohort:- mRNA:AZD2816
    Number of subjects analysed
    280
    277
    Units: Percentage of participants
        number (confidence interval 95%)
    57.50 (51.48 to 63.36)
    80.51 (75.34 to 85.00)
    Statistical analysis title
    Seroresponse Difference
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Booster Cohort:- mRNA:AZD2816 v Booster Cohort:- mRNA:AZD1222
    Number of subjects included in analysis
    557
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [56]
    Method
    Parameter type
    Seroresponse difference
    Point estimate
    23.01
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    15.41
         upper limit
    30.23
    Notes
    [56] - Non-inferiority was demonstrated if the lower limit of the 2-sided 95% CI rate difference in seroresponse between the comparator group and reference group was > or =-10%.

    Secondary: Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Booster Cohort:- mRNA:AZD2816 and AZD1222 in Historical Control

    Close Top of page
    End point title
    Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Booster Cohort:- mRNA:AZD2816 and AZD1222 in Historical Control [57]
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as >= 4-fold increase in the GMT of nAb from baseline. Booster Cohort:- mRNA:AZD2816 is the comparator group and AZD1222 in Historical Control is the reference group, both compared for response against the original Wuhan-Hu-1 strain. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    Booster Cohort: 28 days after booster dose (Day 29) and Historical Control: 28 days after the second dose (Day 57)
    Notes
    [57] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Booster Cohort:- mRNA:AZD2816 Historical Control
    Number of subjects analysed
    277
    508
    Units: Percentage of participants
        number (confidence interval 95%)
    49.82 (43.78 to 55.86)
    84.06 (80.58 to 87.13)
    Statistical analysis title
    Seroresponse Difference
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Booster Cohort:- mRNA:AZD2816 v Historical Control
    Number of subjects included in analysis
    785
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [58]
    Method
    Parameter type
    Seroresponse difference
    Point estimate
    -34.24
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -40.77
         upper limit
    -27.45
    Notes
    [58] - Non-inferiority was demonstrated if the lower limit of the 2-sided 95% CI rate difference in seroresponse between the comparator group and reference group was > or =-10%.

    Secondary: Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Booster Cohort:- mRNA:AZD2816 and Booster Cohort:- mRNA:AZD1222

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    End point title
    Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Booster Cohort:- mRNA:AZD2816 and Booster Cohort:- mRNA:AZD1222 [59]
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as >= 4-fold increase in the GMT of nAb from baseline. Booster Cohort:- mRNA:AZD2816 is the comparator group and Booster Cohort:- mRNA:AZD1222 is the reference group, both compared for response against the original Wuhan-Hu-1 strain. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    28 days after booster dose (Day 29)
    Notes
    [59] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Booster Cohort:- mRNA:AZD1222 Booster Cohort:- mRNA:AZD2816
    Number of subjects analysed
    280
    277
    Units: Percentage of participants
        number (confidence interval 95%)
    42.86 (36.99 to 48.88)
    49.82 (43.78 to 55.86)
    Statistical analysis title
    Seroresponse Difference
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Booster Cohort:- mRNA:AZD2816 v Booster Cohort:- mRNA:AZD1222
    Number of subjects included in analysis
    557
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [60]
    Method
    Parameter type
    Seroresponse difference
    Point estimate
    6.96
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.31
         upper limit
    15.1
    Notes
    [60] - Non-inferiority was demonstrated if the lower limit of the 2-sided 95% CI rate difference in seroresponse between the comparator group and reference group was > or =-10%.

    Secondary: Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- mRNA:AZD2816 and Primary Vaccination Cohort:- AZD1222 (4)

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    End point title
    Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- mRNA:AZD2816 and Primary Vaccination Cohort:- AZD1222 (4) [61]
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as >= 4-fold increase in the GMT of nAb from baseline. Booster Cohort:- mRNA:AZD2816 is the comparator group and Primary Vaccination Cohort:- AZD1222 (4) is the reference group, both compared for response against B.1.351 variant. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    Booster Cohort: 28 days after booster dose (Day 29) and Primary Vaccination Cohort: 28 days after the second dose (Day 57)
    Notes
    [61] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Primary Vaccination Cohort:- AZD1222 (4) Booster Cohort:- mRNA:AZD2816
    Number of subjects analysed
    344
    277
    Units: Percentage of participants
        number (confidence interval 95%)
    51.45 (46.03 to 56.85)
    80.51 (75.34 to 85.00)
    Statistical analysis title
    Seroresponse Difference
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Booster Cohort:- mRNA:AZD2816 v Primary Vaccination Cohort:- AZD1222 (4)
    Number of subjects included in analysis
    621
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [62]
    Method
    Parameter type
    Seroresponse difference
    Point estimate
    29.05
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    21.76
         upper limit
    35.81
    Notes
    [62] - Non-inferiority was demonstrated if the lower limit of the 2-sided 95% CI rate difference in seroresponse between the comparator group and reference group was > or =-10%.

    Secondary: Number of Participants With TESAEs, MAAEs, and AESIs From Day 1 Through 6 Months Post Last Dose

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    End point title
    Number of Participants With TESAEs, MAAEs, and AESIs From Day 1 Through 6 Months Post Last Dose [63]
    End point description
    TEAEs: AEs present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. SAE: an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. MAAEs: AEs leading to medically-attended visits that were unscheduled visits to or from medical doctor for any reason. AESIs: AEs of scientific/medical interest specific to the further understanding of study drug safety profile and require close monitoring and rapid communication by the investigators to the Sponsor. Seronegative safety analysis set: all participants who received at least 1 dose of study treatment, were analysed according to treatment actually received, and were seronegative at baseline.
    End point type
    Secondary
    End point timeframe
    During the 6 months follow-up period after vaccination (vaccines administered on Days 1 and 29 or Day 85 [only for primary vaccination cohorts])
    Notes
    [63] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Primary Vaccination Cohort:- AZD2816 (4) Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) Primary Vaccination Cohort:- AZD2816 (12) Booster Cohort:- AZD1222:AZD1222 Booster Cohort:- AZD1222:AZD2816 Booster Cohort:- mRNA:AZD1222 Booster Cohort:- mRNA:AZD2816
    Number of subjects analysed
    379
    380
    191
    349
    348
    300
    302
    Units: Participants
        Any TESAEs
    2
    5
    2
    6
    7
    3
    4
        Any MAAEs
    69
    82
    50
    72
    65
    47
    58
        Any AESIs
    48
    51
    32
    41
    42
    31
    33
    No statistical analyses for this end point

    Secondary: GMT of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) and Primary Vaccination Cohort:- AZD1222 (4)

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    End point title
    GMT of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) and Primary Vaccination Cohort:- AZD1222 (4) [64]
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. The GMT was calculated as antilogarithm of Σ(log base 2 transformed titre/n), i.e. as anti-logarithm transformation of the mean of log-transformed titre, where 'n' was the number of participants with titre information. Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) is the comparator group and Primary Vaccination Cohort:- AZD1222 (4) is the reference group, both compared for response against the Original Wuhan-Hu-1 Strain. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    28 days after second dose (Day 57)
    Notes
    [64] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Primary Vaccination Cohort:- AZD1222 (4) Primary Vaccination Cohort:- AZD1222 + AZD2816 (4)
    Number of subjects analysed
    348
    334
    Units: 1/dilution
        geometric mean (confidence interval 95%)
    769.03 (731.95 to 808.00)
    581.78 (553.12 to 611.92)
    Statistical analysis title
    GMT Ratio
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) v Primary Vaccination Cohort:- AZD1222 (4)
    Number of subjects included in analysis
    682
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [65]
    Method
    Parameter type
    GMT ratio
    Point estimate
    0.76
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.7
         upper limit
    0.81
    Notes
    [65] - Noninferiority was demonstrated if the lower limit of the 2-sided 95% CI of the GMT ratio of the comparator group and reference group was > 0.67.

    Secondary: GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) and Primary Vaccination Cohort:- AZD1222 (4)

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    End point title
    GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) and Primary Vaccination Cohort:- AZD1222 (4) [66]
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) is the comparator group and Primary Vaccination Cohort:- AZD1222 (4) is the reference group, both compared for response against B.1.351 variant. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    28 days after second dose (Day 57)
    Notes
    [66] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Primary Vaccination Cohort:- AZD1222 (4) Primary Vaccination Cohort:- AZD1222 + AZD2816 (4)
    Number of subjects analysed
    348
    334
    Units: 1/dilution
        geometric mean (confidence interval 95%)
    329.46 (319.47 to 339.76)
    446.63 (432.91 to 460.78)
    Statistical analysis title
    GMT Ratio
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) v Primary Vaccination Cohort:- AZD1222 (4)
    Number of subjects included in analysis
    682
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [67]
    Method
    Parameter type
    GMT ratio
    Point estimate
    1.36
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.3
         upper limit
    1.42
    Notes
    [67] - Noninferiority was demonstrated if the lower limit of the 2-sided 95% CI of the GMT ratio of the comparator group and reference group was > 0.67.

    Secondary: Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Primary Vaccination Cohort:- AZD2816 (4) and Primary Vaccination Cohort:- AZD1222 (4)

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    End point title
    Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Primary Vaccination Cohort:- AZD2816 (4) and Primary Vaccination Cohort:- AZD1222 (4) [68]
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as >= 4-fold increase in the GMT of nAb from baseline. Primary Vaccination Cohort:- AZD2816 (4) is the comparator group and Primary Vaccination Cohort:- AZD1222 (4) is the reference group, both compared for response against B.1.351 variant. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame. The arbitrary number 999 signified the upper limit of 95% confidence interval was not evaluable as all participants had seroresponse for the specified arm.
    End point type
    Secondary
    End point timeframe
    28 days after second dose (Day 57)
    Notes
    [68] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Primary Vaccination Cohort:- AZD1222 (4) Primary Vaccination Cohort:- AZD2816 (4)
    Number of subjects analysed
    344
    342
    Units: Percentage of participants
        number (confidence interval 95%)
    99.42 (97.92 to 99.93)
    100 (98.73 to 999)
    Statistical analysis title
    Seroresponse Difference
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Primary Vaccination Cohort:- AZD2816 (4) v Primary Vaccination Cohort:- AZD1222 (4)
    Number of subjects included in analysis
    686
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [69]
    Method
    Parameter type
    Seroresponse difference
    Point estimate
    0.58
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.61
         upper limit
    2.09
    Notes
    [69] - Non-inferiority was demonstrated if the lower limit of the 2-sided 95% CI rate difference in seroresponse between the comparator group and reference group was > or =-10%.

    Secondary: GMT of SARS-CoV-2 nAb Against the B.1.351 Variant and the Original Wuhan-Hu-1 Strain by Primary Vaccination Cohort:- AZD1222 + AZD2816 (4)

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    End point title
    GMT of SARS-CoV-2 nAb Against the B.1.351 Variant and the Original Wuhan-Hu-1 Strain by Primary Vaccination Cohort:- AZD1222 + AZD2816 (4)
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. GMT was calculated as antilogarithm of Σ(log base 2 transformed titre/n), i.e. as anti-logarithm transformation of mean of log-transformed titre, where 'n' was number of participants with titre information. Primary Vaccination Cohort:-AZD1222+AZD2816 (4) with response against B.1.351 variant is comparator group and Primary Vaccination Cohort:-AZD1222+AZD2816 (4) with response against the original Wuhan-Hu-1 strain is reference group. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, no protocol deviations judged to have potential to interfere with antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    28 days after second dose (Day 57)
    End point values
    Primary Vaccination Cohort:- AZD1222+AZD2816 (4) (Comparator) Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) (Reference)
    Number of subjects analysed
    334
    334
    Units: 1/dilution
        geometric mean (confidence interval 95%)
    392.13 (380.34 to 404.28)
    586.00 (566.15 to 606.54)
    Statistical analysis title
    GMT Ratio
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Primary Vaccination Cohort:- AZD1222+AZD2816 (4) (Comparator) v Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) (Reference)
    Number of subjects included in analysis
    668
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [70]
    Method
    Parameter type
    GMT ratio
    Point estimate
    0.67
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.64
         upper limit
    0.7
    Notes
    [70] - Noninferiority was demonstrated if the lower limit of the 2-sided 95% CI of the GMT ratio of the comparator group and reference group was > 0.67.

    Secondary: GMT of SARS-CoV-2 nAb Against B.1.351 Variant and the Original Wuhan-Hu-1 Strain Elicited by Primary Vaccination Cohort:- AZD2816 (4)

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    End point title
    GMT of SARS-CoV-2 nAb Against B.1.351 Variant and the Original Wuhan-Hu-1 Strain Elicited by Primary Vaccination Cohort:- AZD2816 (4)
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. GMT was calculated as antilogarithm of Σ(log base 2 transformed titre/n), i.e. as anti-logarithm transformation of the mean of log-transformed titre, where 'n' was the number of participants with titre information. Primary Vaccination Cohort:- AZD2816 (4) with response against B.1.351 variant is comparator group and Primary Vaccination Cohort:- AZD2816 (4) with response against the original Wuhan-Hu-1 strain is reference group. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    28 days after second dose (Day 57)
    End point values
    Primary Vaccination Cohort:- AZD2816 (4) (Comparator) Primary Vaccination Cohort:- AZD2816 (4) (Reference)
    Number of subjects analysed
    342
    342
    Units: 1/dilution
        geometric mean (confidence interval 95%)
    718.10 (662.58 to 778.27)
    185.70 (168.16 to 205.07)
    Statistical analysis title
    GMT Ratio
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Primary Vaccination Cohort:- AZD2816 (4) (Comparator) v Primary Vaccination Cohort:- AZD2816 (4) (Reference)
    Number of subjects included in analysis
    684
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [71]
    Method
    Parameter type
    GMT ratio
    Point estimate
    3.87
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    3.4
         upper limit
    4.39
    Notes
    [71] - Noninferiority was demonstrated if the lower limit of the 2-sided 95% CI of the GMT ratio of the comparator group and reference group was > 0.67.

    Secondary: Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Primary Vaccination Cohort:- AZD2816 (4) and Primary Vaccination Cohort:- AZD1222 (4)

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    End point title
    Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Primary Vaccination Cohort:- AZD2816 (4) and Primary Vaccination Cohort:- AZD1222 (4) [72]
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as >= 4-fold increase in the GMT of nAb from baseline. Primary Vaccination Cohort:- AZD2816 (4) is the comparator group and Primary Vaccination Cohort:- AZD1222 (4) is the reference group, both compared for response against the original Wuhan-Hu-1 strain. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    28 days after second dose (Day 57)
    Notes
    [72] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Primary Vaccination Cohort:- AZD1222 (4) Primary Vaccination Cohort:- AZD2816 (4)
    Number of subjects analysed
    344
    342
    Units: Percentage of participants
        number (confidence interval 95%)
    84.59 (80.34 to 88.24)
    49.42 (44.00 to 54.85)
    Statistical analysis title
    Seroresponse Difference
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Primary Vaccination Cohort:- AZD2816 (4) v Primary Vaccination Cohort:- AZD1222 (4)
    Number of subjects included in analysis
    686
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [73]
    Method
    Parameter type
    Seroresponse difference
    Point estimate
    -35.18
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -41.46
         upper limit
    -28.44
    Notes
    [73] - Non-inferiority was demonstrated if the lower limit of the 2-sided 95% CI rate difference in seroresponse between the comparator group and reference group was > or =-10%.

    Secondary: Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) and the Original Wuhan Hu-1 Strain Elicited by Primary Vaccination Cohort:- AZD1222 (4)

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    End point title
    Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) and the Original Wuhan Hu-1 Strain Elicited by Primary Vaccination Cohort:- AZD1222 (4) [74]
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as >= 4-fold increase in the GMT of nAb from baseline. Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) with response against B.1.351 variant is the comparator group and Primary Vaccination Cohort:- AZD1222 (4) with response against the original Wuhan-Hu-1 strain is the reference group. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    28 days after second dose (Day 57)
    Notes
    [74] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Primary Vaccination Cohort:- AZD1222 (4) Primary Vaccination Cohort:- AZD1222 + AZD2816 (4)
    Number of subjects analysed
    344
    334
    Units: Percentage of participants
        number (confidence interval 95%)
    87.50 (83.53 to 90.80)
    62.57 (57.14 to 67.78)
    Statistical analysis title
    Seroresponse Difference
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) v Primary Vaccination Cohort:- AZD1222 (4)
    Number of subjects included in analysis
    678
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [75]
    Method
    Parameter type
    Seroresponse difference
    Point estimate
    -24.93
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -31.06
         upper limit
    -18.56
    Notes
    [75] - Non-inferiority was demonstrated if the lower limit of the 2-sided 95% CI rate difference in seroresponse between the comparator group and reference group was > or =-10%.

    Secondary: Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) and Primary Vaccination Cohort:- AZD1222 (4)

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    End point title
    Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) and Primary Vaccination Cohort:- AZD1222 (4) [76]
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as >= 4-fold increase in the GMT of nAb from baseline. Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) is the comparator group and Primary Vaccination Cohort:- AZD1222 (4) is the reference group, both compared for response against B.1.351 variant. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    28 days after second dose (Day 57)
    Notes
    [76] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Primary Vaccination Cohort:- AZD1222 (4) Primary Vaccination Cohort:- AZD1222 + AZD2816 (4)
    Number of subjects analysed
    344
    334
    Units: Percentage of participants
        number (confidence interval 95%)
    99.42 (97.92 to 99.93)
    99.40 (97.85 to 99.93)
    Statistical analysis title
    Seroresponse Difference
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) v Primary Vaccination Cohort:- AZD1222 (4)
    Number of subjects included in analysis
    678
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [77]
    Method
    Parameter type
    Seroresponse difference
    Point estimate
    -0.02
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.63
         upper limit
    1.56
    Notes
    [77] - Non-inferiority was demonstrated if the lower limit of the 2-sided 95% CI rate difference in seroresponse between the comparator group and reference group was > or =-10%.

    Secondary: Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) and Primary Vaccination Cohort:- AZD1222 (4)

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    End point title
    Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) and Primary Vaccination Cohort:- AZD1222 (4) [78]
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as >= 4-fold increase in the GMT of nAb from baseline. Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) is the comparator group and Primary Vaccination Cohort:- AZD1222 (4) is the reference group, both compared for response against the original Wuhan-Hu-1 strain. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    28 days after second dose (Day 57)
    Notes
    [78] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Primary Vaccination Cohort:- AZD1222 (4) Primary Vaccination Cohort:- AZD1222 + AZD2816 (4)
    Number of subjects analysed
    344
    334
    Units: Percentage of participants
        number (confidence interval 95%)
    99.42 (97.92 to 99.93)
    80.24 (75.56 to 84.38)
    Statistical analysis title
    Seroresponse Difference
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) v Primary Vaccination Cohort:- AZD1222 (4)
    Number of subjects included in analysis
    678
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [79]
    Method
    Parameter type
    Seroresponse difference
    Point estimate
    -19.18
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -23.8
         upper limit
    -14.98
    Notes
    [79] - Non-inferiority was demonstrated if the lower limit of the 2-sided 95% CI rate difference in seroresponse between the comparator group and reference group was > or =-10%.

    Secondary: Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant and the Original Wuhan-Hu-1 Strain Elicited by Primary Vaccination Cohort:- AZD1222 + AZD2816 (4)

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    End point title
    Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant and the Original Wuhan-Hu-1 Strain Elicited by Primary Vaccination Cohort:- AZD1222 + AZD2816 (4)
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as >= 4-fold increase in the GMT of nAb from baseline. Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) with response against B.1.351 variant is the comparator group and Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) with response against the original Wuhan-Hu-1 strain is the reference group. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    28 days after second dose (Day 57)
    End point values
    Primary Vaccination Cohort:- AZD1222+AZD2816 (4) (Comparator) Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) (Reference)
    Number of subjects analysed
    334
    334
    Units: Percentage of participants
        number (confidence interval 95%)
    99.40 (97.85 to 99.93)
    99.40 (97.85 to 99.93)
    Statistical analysis title
    Seroresponse Difference
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Primary Vaccination Cohort:- AZD1222+AZD2816 (4) (Comparator) v Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) (Reference)
    Number of subjects included in analysis
    668
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [80]
    Method
    Parameter type
    Seroresponse difference
    Point estimate
    0
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.62
         upper limit
    1.62
    Notes
    [80] - Non-inferiority was demonstrated if the lower limit of the 2-sided 95% CI rate difference in seroresponse between the comparator group and reference group was > or =-10%.

    Secondary: Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant and the Original Wuhan-Hu-1 Strain Elicited by Primary Vaccination Cohort:- AZD2816 (4)

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    End point title
    Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant and the Original Wuhan-Hu-1 Strain Elicited by Primary Vaccination Cohort:- AZD2816 (4)
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as >= 4-fold increase in the GMT of nAb from baseline. Primary Vaccination Cohort:- AZD2816 (4) with response against B.1.351 variant is the comparator group and Primary Vaccination Cohort:- AZD2816 (4) with response against the original Wuhan-Hu-1 strain is the reference group. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    28 days after second dose (Day 57)
    End point values
    Primary Vaccination Cohort:- AZD2816 (4) (Comparator) Primary Vaccination Cohort:- AZD2816 (4) (Reference)
    Number of subjects analysed
    342
    342
    Units: Percentage of participants
        number (confidence interval 95%)
    88.60 (84.74 to 91.76)
    49.42 (44.00 to 54.85)
    Statistical analysis title
    Seroresponse Difference
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Primary Vaccination Cohort:- AZD2816 (4) (Comparator) v Primary Vaccination Cohort:- AZD2816 (4) (Reference)
    Number of subjects included in analysis
    684
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [81]
    Method
    Parameter type
    Seroresponse difference
    Point estimate
    39.18
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    32.68
         upper limit
    45.21
    Notes
    [81] - Non-inferiority was demonstrated if the lower limit of the 2-sided 95% CI rate difference in seroresponse between the comparator group and reference group was > or =-10%.

    Secondary: GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- AZD1222:AZD1222 and Primary Vaccination Cohort:- AZD1222 (4)

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    End point title
    GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- AZD1222:AZD1222 and Primary Vaccination Cohort:- AZD1222 (4) [82]
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Booster Cohort:- AZD1222:AZD1222 is the comparator group and Primary Vaccination Cohort:- AZD1222 (4) is the reference group, both compared for response against B.1.351 variant. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    Booster Cohort: 28 days after booster dose (Day 29) and Primary Vaccination Cohort: 28 days after the second dose (Day 57)
    Notes
    [82] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Primary Vaccination Cohort:- AZD1222 (4) Booster Cohort:- AZD1222:AZD1222
    Number of subjects analysed
    348
    329
    Units: 1/dilution
        geometric mean (confidence interval 95%)
    360.43 (324.90 to 399.84)
    185.70 (169.32 to 203.66)
    Statistical analysis title
    GMT Ratio
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Booster Cohort:- AZD1222:AZD1222 v Primary Vaccination Cohort:- AZD1222 (4)
    Number of subjects included in analysis
    677
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [83]
    Method
    Parameter type
    GMT ratio
    Point estimate
    0.52
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.45
         upper limit
    0.59
    Notes
    [83] - Noninferiority was demonstrated if the lower limit of the 2-sided 95% CI of the GMT ratio of the comparator group and reference group was > 0.67.

    Secondary: GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- AZD1222:AZD1222 and the Original Wuhan-Hu-1 Strain Elicited by AZD1222 in Historical Control

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    End point title
    GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- AZD1222:AZD1222 and the Original Wuhan-Hu-1 Strain Elicited by AZD1222 in Historical Control [84]
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. GMT was calculated as antilogarithm of Σ(log base 2 transformed titre/n), i.e. as anti-logarithm transformation of the mean of log-transformed titre, where 'n' was the number of participants with titre information. Booster Cohort:- AZD1222:AZD1222 with response against B.1.351 variant is the comparator group and AZD1222 in Historical Control with response against the original Wuhan-Hu-1 strain is the reference group. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    Booster Cohort: 28 days after booster dose (Day 29) and Historical Control: 28 days after the second dose (Day 57)
    Notes
    [84] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Booster Cohort:- AZD1222:AZD1222 Historical Control
    Number of subjects analysed
    329
    508
    Units: 1/dilution
        geometric mean (confidence interval 95%)
    185.70 (169.32 to 203.66)
    242.80 (224.82 to 262.23)
    Statistical analysis title
    GMT Ratio
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Booster Cohort:- AZD1222:AZD1222 v Historical Control
    Number of subjects included in analysis
    837
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [85]
    Method
    Parameter type
    GMT ratio
    Point estimate
    0.76
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.68
         upper limit
    0.86
    Notes
    [85] - Noninferiority was demonstrated if the lower limit of the 2-sided 95% CI of the GMT ratio of the comparator group and reference group was > 0.67.

    Secondary: GMT of SARS-CoV-2 nAb Against the B.1.351 Variant and the Original Wuhan-Hu-1 Strain by Booster Cohort:- AZD1222:AZD2816

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    End point title
    GMT of SARS-CoV-2 nAb Against the B.1.351 Variant and the Original Wuhan-Hu-1 Strain by Booster Cohort:- AZD1222:AZD2816
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. GMT was calculated as antilogarithm of Σ(log base 2 transformed titre/n), i.e. as anti-logarithm transformation of the mean of log-transformed titre, where 'n' was the number of participants with titre information. Booster Cohort:- AZD1222:AZD2816 with response against B.1.351 variant is the comparator group and Booster Cohort:- AZD1222:AZD2816 with response against the original Wuhan-Hu-1 strain is the reference group. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    28 days after second dose (Day 57)
    End point values
    Booster Cohort:- AZD1222:AZD2816 (Comparator) Booster Cohort:- AZD1222:AZD2816 (Reference)
    Number of subjects analysed
    322
    322
    Units: 1/dilution
        geometric mean (confidence interval 95%)
    341.96 (315.48 to 370.66)
    213.26 (197.45 to 230.34)
    Statistical analysis title
    GMT Ratio
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Booster Cohort:- AZD1222:AZD2816 (Comparator) v Booster Cohort:- AZD1222:AZD2816 (Reference)
    Number of subjects included in analysis
    644
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [86]
    Method
    Parameter type
    GMT ratio
    Point estimate
    1.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.43
         upper limit
    1.79
    Notes
    [86] - Noninferiority was demonstrated if the lower limit of the 2-sided 95% CI of the GMT ratio of the comparator group and reference group was > 0.67.

    Secondary: GMT of SARS-CoV-2 nAb Against the B.1.351 Variant and the Original Wuhan-Hu-1 Strain by Booster Cohort:- AZD1222:AZD1222

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    End point title
    GMT of SARS-CoV-2 nAb Against the B.1.351 Variant and the Original Wuhan-Hu-1 Strain by Booster Cohort:- AZD1222:AZD1222
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. GMT was calculated as antilogarithm of Σ(log base 2 transformed titre/n), i.e. as anti-logarithm transformation of the mean of log-transformed titre, where 'n' was the number of participants with titre information.Booster Cohort:- AZD1222:AZD1222 with response against B.1.351 variant is comparator group and Booster Cohort:- AZD1222:AZD1222 with response against the original Wuhan-Hu-1 strain is reference group. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    28 days after second dose (Day 57)
    End point values
    Booster Cohort:- AZD1222:AZD1222 (Comparator) Booster Cohort:- AZD1222:AZD1222 (Reference)
    Number of subjects analysed
    329
    329
    Units: 1/dilution
        geometric mean (confidence interval 95%)
    185.70 (169.32 to 203.66)
    246.45 (227.39 to 267.12)
    Statistical analysis title
    GMT Ratio
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Booster Cohort:- AZD1222:AZD1222 (Comparator) v Booster Cohort:- AZD1222:AZD1222 (Reference)
    Number of subjects included in analysis
    658
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [87]
    Method
    Parameter type
    GMT ratio
    Point estimate
    0.75
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.67
         upper limit
    0.85
    Notes
    [87] - Noninferiority was demonstrated if the lower limit of the 2-sided 95% CI of the GMT ratio of the comparator group and reference group was > 0.67.

    Secondary: Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Booster Cohort:- AZD1222:AZD1222 and AZD1222 in Historical Control

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    End point title
    Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Booster Cohort:- AZD1222:AZD1222 and AZD1222 in Historical Control [88]
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as >= 4-fold increase in the GMT of nAb from baseline. Booster Cohort:- AZD1222:AZD1222 is the comparator group and AZD1222 in Historical Control is the reference group, both compared for response against the original Wuhan-Hu-1 strain. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    Booster Cohort: 28 days after booster dose (Day 29) and Historical Control: 28 days after the second dose (Day 57)
    Notes
    [88] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Booster Cohort:- AZD1222:AZD1222 Historical Control
    Number of subjects analysed
    329
    508
    Units: Percentage of participants
        number (confidence interval 95%)
    65.96 (60.56 to 71.07)
    84.06 (80.58 to 87.13)
    Statistical analysis title
    Seroresponse Difference
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Booster Cohort:- AZD1222:AZD1222 v Historical Control
    Number of subjects included in analysis
    837
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [89]
    Method
    Parameter type
    Seroresponse difference
    Point estimate
    -18.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -24.13
         upper limit
    -12.1
    Notes
    [89] - Non-inferiority was demonstrated if the lower limit of the 2-sided 95% CI rate difference in seroresponse between the comparator group and reference group was > or =-10%.

    Secondary: Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant and the Original Wuhan-Hu-1 Strain Elicited by Booster Cohort:- AZD1222:AZD2816

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    End point title
    Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant and the Original Wuhan-Hu-1 Strain Elicited by Booster Cohort:- AZD1222:AZD2816
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as >= 4-fold increase in the GMT of nAb from baseline. Booster Cohort:- AZD1222:AZD2816 with response against B.1.351 variant is the comparator group and Booster Cohort:- AZD1222:AZD2816 with response against the original Wuhan-Hu-1 strain is the reference group. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    28 days after second dose (Day 57)
    End point values
    Booster Cohort:- AZD1222:AZD2816 (Comparator) Booster Cohort:- AZD1222:AZD2816 (Reference)
    Number of subjects analysed
    320
    320
    Units: Percentage of participants
        number (confidence interval 95%)
    82.81 (78.22 to 86.78)
    65.94 (60.46 to 71.12)
    Statistical analysis title
    Seroresponse Difference
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Booster Cohort:- AZD1222:AZD2816 (Comparator) v Booster Cohort:- AZD1222:AZD2816 (Reference)
    Number of subjects included in analysis
    640
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [90]
    Method
    Parameter type
    Seroresponse difference
    Point estimate
    16.87
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    10.15
         upper limit
    23.4
    Notes
    [90] - Non-inferiority was demonstrated if the lower limit of the 2-sided 95% CI rate difference in seroresponse between the comparator group and reference group was > or =-10%.

    Secondary: Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- AZD1222:AZD1222 and the Original Wuhan-Hu-1 Strain Elicited by AZD1222 in Historical Control

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    End point title
    Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- AZD1222:AZD1222 and the Original Wuhan-Hu-1 Strain Elicited by AZD1222 in Historical Control [91]
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as >= 4-fold increase in the GMT of nAb from baseline. Booster Cohort:- AZD1222:AZD1222 with response against B.1.351 variant is the comparator group and AZD1222 in Historical Control with response against the original Wuhan-Hu-1 strain is the reference group. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    Booster Cohort: 28 days after booster dose (Day 29) and Historical Control: 28 days after the second dose (Day 57)
    Notes
    [91] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Booster Cohort:- AZD1222:AZD1222 Historical Control
    Number of subjects analysed
    329
    508
    Units: Percentage of participants
        number (confidence interval 95%)
    65.96 (60.56 to 71.07)
    84.06 (80.58 to 87.13)
    Statistical analysis title
    Seroresponse Difference
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Booster Cohort:- AZD1222:AZD1222 v Historical Control
    Number of subjects included in analysis
    837
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [92]
    Method
    Parameter type
    Seroresponse difference
    Point estimate
    -18.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -24.13
         upper limit
    -12.1
    Notes
    [92] - Non-inferiority was demonstrated if the lower limit of the 2-sided 95% CI rate difference in seroresponse between the comparator group and reference group was > or =-10%.

    Secondary: Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- AZD1222:AZD1222 and Primary Vaccination Cohort:- AZD1222 (4)

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    End point title
    Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- AZD1222:AZD1222 and Primary Vaccination Cohort:- AZD1222 (4) [93]
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as >= 4-fold increase in the GMT of nAb from baseline. Booster Cohort:- AZD1222:AZD1222 is the comparator group and Primary Vaccination Cohort:- AZD1222 (4) is the reference group, both compared for response against B.1.351 Variant. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    Booster Cohort: 28 days after booster dose (Day 29) and Primary Vaccination Cohort: 28 days after the second dose (Day 57)
    Notes
    [93] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Primary Vaccination Cohort:- AZD1222 (4) Booster Cohort:- AZD1222:AZD1222
    Number of subjects analysed
    344
    329
    Units: Percentage of participants
        number (confidence interval 95%)
    51.45 (46.03 to 56.85)
    65.96 (60.56 to 71.07)
    Statistical analysis title
    Seroresponse Difference
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Booster Cohort:- AZD1222:AZD1222 v Primary Vaccination Cohort:- AZD1222 (4)
    Number of subjects included in analysis
    673
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [94]
    Method
    Parameter type
    Seroresponse difference
    Point estimate
    14.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    7.07
         upper limit
    21.71
    Notes
    [94] - Non-inferiority was demonstrated if the lower limit of the 2-sided 95% CI rate difference in seroresponse between the comparator group and reference group was > or =-10%.

    Secondary: Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant and the Original Wuhan-Hu-1 Strain Elicited by Booster Cohort:- AZD1222:AZD1222

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    End point title
    Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant and the Original Wuhan-Hu-1 Strain Elicited by Booster Cohort:- AZD1222:AZD1222
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as >= 4-fold increase in the GMT of nAb from baseline. Booster Cohort:- AZD1222:AZD1222 with response against B.1.351 variant is the comparator group and Booster Cohort:- AZD1222:AZD1222 with response against the original Wuhan-Hu-1 strain is the reference group. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    28 days after second dose (Day 57)
    End point values
    Booster Cohort:- AZD1222:AZD1222 (Comparator) Booster Cohort:- AZD1222:AZD1222 (Reference)
    Number of subjects analysed
    329
    329
    Units: Percentage of participants
        number (confidence interval 95%)
    65.96 (60.56 to 71.07)
    65.96 (60.56 to 71.07)
    Statistical analysis title
    Seroresponse Difference
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Booster Cohort:- AZD1222:AZD1222 (Comparator) v Booster Cohort:- AZD1222:AZD1222 (Reference)
    Number of subjects included in analysis
    658
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [95]
    Method
    Parameter type
    Seroresponse difference
    Point estimate
    0
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -7.21
         upper limit
    7.21
    Notes
    [95] - Non-inferiority was demonstrated if the lower limit of the 2-sided 95% CI rate difference in seroresponse between the comparator group and reference group was > or =-10%.

    Secondary: GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- mRNA:AZD1222 and Primary Vaccination Cohort:- AZD1222 (4)

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    End point title
    GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- mRNA:AZD1222 and Primary Vaccination Cohort:- AZD1222 (4) [96]
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. GMT was calculated as antilogarithm of Σ(log base 2 transformed titre/n), i.e. as anti-logarithm transformation of the mean of log-transformed titre, where 'n' was the number of participants with titre information. Booster Cohort:- mRNA:AZD1222 is the comparator group and Primary Vaccination Cohort:- AZD1222 (4) is the reference group, both compared for response against B.1.351 variant. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    Booster Cohort: 28 days after booster dose (Day 29) and Primary Vaccination Cohort: 28 days after the second dose (Day 57)
    Notes
    [96] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Primary Vaccination Cohort:- AZD1222 (4) Booster Cohort:- mRNA:AZD1222
    Number of subjects analysed
    348
    280
    Units: 1/dilution
        geometric mean (confidence interval 95%)
    360.43 (324.90 to 399.84)
    718.90 (670.46 to 770.84)
    Statistical analysis title
    GMT Ratio
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Booster Cohort:- mRNA:AZD1222 v Primary Vaccination Cohort:- AZD1222 (4)
    Number of subjects included in analysis
    628
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [97]
    Method
    Parameter type
    GMT ratio
    Point estimate
    2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.75
         upper limit
    2.28
    Notes
    [97] - Noninferiority was demonstrated if the lower limit of the 2-sided 95% CI of the GMT ratio of the comparator group and reference group was > 0.67.

    Secondary: GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- mRNA:AZD1222 and the Original Wuhan-Hu-1 Strain Elicited by AZD1222 in Historical Control

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    End point title
    GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- mRNA:AZD1222 and the Original Wuhan-Hu-1 Strain Elicited by AZD1222 in Historical Control [98]
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Booster Cohort:- mRNA:AZD1222 with response against B.1.351 variant is the comparator group and AZD1222 in Historical Control with response against the original Wuhan-Hu-1 strain is the reference group. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    Booster Cohort: 28 days after booster dose (Day 29) and Historical Control: 28 days after the second dose (Day 57)
    Notes
    [98] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Booster Cohort:- mRNA:AZD1222 Historical Control
    Number of subjects analysed
    280
    508
    Units: 1/dilution
        geometric mean (confidence interval 95%)
    718.90 (670.46 to 770.84)
    242.80 (224.82 to 262.23)
    Statistical analysis title
    GMT Ratio
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Booster Cohort:- mRNA:AZD1222 v Historical Control
    Number of subjects included in analysis
    788
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [99]
    Method
    Parameter type
    GMT ratio
    Point estimate
    2.96
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.64
         upper limit
    3.32
    Notes
    [99] - Noninferiority was demonstrated if the lower limit of the 2-sided 95% CI of the GMT ratio of the comparator group and reference group was > 0.67.

    Secondary: GMT of SARS-CoV-2 nAb Against the B.1.351 Variant and the Original Wuhan-Hu-1 Strain by Booster Cohort:- mRNA:AZD2816

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    End point title
    GMT of SARS-CoV-2 nAb Against the B.1.351 Variant and the Original Wuhan-Hu-1 Strain by Booster Cohort:- mRNA:AZD2816
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Booster Cohort:- mRNA:AZD2816 with response against B.1.351 variant is the comparator group and Booster Cohort:- mRNA:AZD2816 with response against the original Wuhan-Hu-1 strain is the reference group. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    28 days after second dose (Day 57)
    End point values
    Booster Cohort:- mRNA:AZD2816 (Comparator) Booster Cohort:- mRNA:AZD2816 (Reference)
    Number of subjects analysed
    280
    280
    Units: 1/dilution
        geometric mean (confidence interval 95%)
    1587.58 (1463.98 to 1721.61)
    1052.73 (974.55 to 1137.19)
    Statistical analysis title
    GMT Ratio
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Booster Cohort:- mRNA:AZD2816 (Comparator) v Booster Cohort:- mRNA:AZD2816 (Reference)
    Number of subjects included in analysis
    560
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [100]
    Method
    Parameter type
    GMT ratio
    Point estimate
    1.51
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.35
         upper limit
    1.69
    Notes
    [100] - Noninferiority was demonstrated if the lower limit of the 2-sided 95% CI of the GMT ratio of the comparator group and reference group was > 0.67.

    Secondary: GMT of SARS-CoV-2 nAb Against the B.1.351 Variant and the Original Wuhan-Hu-1 Strain by Booster Cohort:- mRNA:AZD1222

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    End point title
    GMT of SARS-CoV-2 nAb Against the B.1.351 Variant and the Original Wuhan-Hu-1 Strain by Booster Cohort:- mRNA:AZD1222
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Booster Cohort:- mRNA:AZD1222 with response against B.1.351 variant is the comparator group and Booster Cohort:- mRNA:AZD1222 with response against the original Wuhan-Hu-1 strain is the reference group. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    28 days after second dose (Day 57)
    End point values
    Booster Cohort:- mRNA:AZD1222 (Comparator) Booster Cohort:- mRNA:AZD1222 (Reference)
    Number of subjects analysed
    280
    280
    Units: 1/dilution
        geometric mean (confidence interval 95%)
    718.90 (670.46 to 770.84)
    841.96 (790.34 to 896.96)
    Statistical analysis title
    GMT Ratio
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Booster Cohort:- mRNA:AZD1222 (Comparator) v Booster Cohort:- mRNA:AZD1222 (Reference)
    Number of subjects included in analysis
    560
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [101]
    Method
    Parameter type
    GMT ratio
    Point estimate
    0.85
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.78
         upper limit
    0.94
    Notes
    [101] - Noninferiority was demonstrated if the lower limit of the 2-sided 95% CI of the GMT ratio of the comparator group and reference group was > 0.67.

    Secondary: Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Booster Cohort:- mRNA:AZD1222 and AZD1222 in Historical Control

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    End point title
    Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Booster Cohort:- mRNA:AZD1222 and AZD1222 in Historical Control [102]
    End point description
    Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as >= 4-fold increase in the GMT of nAb from baseline. Booster Cohort:- mRNA:AZD1222 is the comparator group and AZD1222 in Historical Control is the reference group, both compared for response against the original Wuhan-Hu-1 strain. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    Booster Cohort: 28 days after booster dose (Day 29) and Historical Control: 28 days after the second dose (Day 57)
    Notes
    [102] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Booster Cohort:- mRNA:AZD1222 Historical Control
    Number of subjects analysed
    280
    508
    Units: Percentage of participants
        number (confidence interval 95%)
    42.86 (36.99 to 48.88)
    84.06 (80.58 to 87.13)
    Statistical analysis title
    Seroresponse Difference
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Booster Cohort:- mRNA:AZD1222 v Historical Control
    Number of subjects included in analysis
    788
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [103]
    Method
    Parameter type
    Seroresponse difference
    Point estimate
    -41.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -47.57
         upper limit
    -34.41
    Notes
    [103] - Non-inferiority was demonstrated if the lower limit of the 2-sided 95% CI rate difference in seroresponse between the comparator group and reference group was > or =-10%.

    Secondary: Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- mRNA:AZD1222 and Primary Vaccination Cohort:- AZD1222 (4)

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    End point title
    Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- mRNA:AZD1222 and Primary Vaccination Cohort:- AZD1222 (4) [104]
    End point description
    Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as >= 4-fold increase in the GMT of nAb from baseline. Booster Cohort:- mRNA:AZD1222 is the comparator group and Primary Vaccination Cohort:- AZD1222 (4) is the reference group, both compared for response against B.1.351 Variant. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    Booster Cohort: 28 days after booster dose (Day 29) and Primary Vaccination Cohort: 28 days after the second dose (Day 57)
    Notes
    [104] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Primary Vaccination Cohort:- AZD1222 (4) Booster Cohort:- mRNA:AZD1222
    Number of subjects analysed
    344
    280
    Units: Percentage of participants
        number (confidence interval 95%)
    51.45 (46.03 to 56.85)
    57.50 (51.48 to 63.36)
    Statistical analysis title
    Seroresponse Difference
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Booster Cohort:- mRNA:AZD1222 v Primary Vaccination Cohort:- AZD1222 (4)
    Number of subjects included in analysis
    624
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [105]
    Method
    Parameter type
    Seroresponse difference
    Point estimate
    6.05
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.81
         upper limit
    13.77
    Notes
    [105] - Non-inferiority was demonstrated if the lower limit of the 2-sided 95% CI rate difference in seroresponse between the comparator group and reference group was > or =-10%.

    Secondary: Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- mRNA:AZD1222 and the Original Wuhan-Hu-1 Strain Elicited by AZD1222 in Historical Control

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    End point title
    Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- mRNA:AZD1222 and the Original Wuhan-Hu-1 Strain Elicited by AZD1222 in Historical Control [106]
    End point description
    Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as >= 4-fold increase in the GMT of nAb from baseline. Booster Cohort:- mRNA:AZD1222 with response against B.1.351 variant is the comparator group and AZD1222 in Historical Control with response against the original Wuhan-Hu-1 strain is the reference group. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    Booster Cohort: 28 days after booster dose (Day 29) and Historical Control: 28 days after the second dose (Day 57)
    Notes
    [106] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Booster Cohort:- mRNA:AZD1222 Historical Control
    Number of subjects analysed
    280
    508
    Units: Percentage of participants
        number (confidence interval 95%)
    57.50 (51.48 to 63.36)
    84.06 (80.58 to 87.13)
    Statistical analysis title
    Seroresponse Difference
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Booster Cohort:- mRNA:AZD1222 v Historical Control
    Number of subjects included in analysis
    788
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [107]
    Method
    Parameter type
    Seroresponse difference
    Point estimate
    -26.56
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -33.1
         upper limit
    -19.94
    Notes
    [107] - Non-inferiority was demonstrated if the lower limit of the 2-sided 95% CI rate difference in seroresponse between the comparator group and reference group was > or =-10%.

    Secondary: Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant and the Original Wuhan-Hu-1 Strain Elicited by Booster Cohort:- mRNA:AZD2816

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    End point title
    Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant and the Original Wuhan-Hu-1 Strain Elicited by Booster Cohort:- mRNA:AZD2816
    End point description
    Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as >= 4-fold increase in the GMT of nAb from baseline. Booster Cohort:- mRNA:AZD2816 with response against B.1.351 variant is the comparator group and Booster Cohort:- mRNA:AZD2816 with response against the original Wuhan-Hu-1 strain is the reference group. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    28 days after second dose (Day 57)
    End point values
    Booster Cohort:- mRNA:AZD2816 (Comparator) Booster Cohort:- mRNA:AZD2816 (Reference)
    Number of subjects analysed
    277
    277
    Units: Percentage of participants
        number (confidence interval 95%)
    80.51 (75.34 to 85.00)
    49.82 (43.78 to 55.86)
    Statistical analysis title
    Seroresponse Difference
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Booster Cohort:- mRNA:AZD2816 (Comparator) v Booster Cohort:- mRNA:AZD2816 (Reference)
    Number of subjects included in analysis
    554
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [108]
    Method
    Parameter type
    Seroresponse difference
    Point estimate
    30.69
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    22.94
         upper limit
    37.9
    Notes
    [108] - Non-inferiority was demonstrated if the lower limit of the 2-sided 95% CI rate difference in seroresponse between the comparator group and reference group was > or =-10%.

    Secondary: Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant and the Original Wuhan-Hu-1 Strain Elicited by Booster Cohort:- mRNA:AZD1222

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    End point title
    Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant and the Original Wuhan-Hu-1 Strain Elicited by Booster Cohort:- mRNA:AZD1222
    End point description
    Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as >= 4-fold increase in the GMT of nAb from baseline. Booster Cohort:- mRNA:AZD1222 with response against B.1.351 variant is the comparator group and Booster Cohort:- mRNA:AZD1222 with response against the original Wuhan-Hu-1 strain is the reference group. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    28 days after second dose (Day 57)
    End point values
    Booster Cohort:- mRNA:AZD1222 (Comparator) Booster Cohort:- mRNA:AZD1222 (Reference)
    Number of subjects analysed
    280
    280
    Units: Percentage of participants
        number (confidence interval 95%)
    57.50 (51.48 to 63.36)
    42.86 (36.99 to 48.88)
    Statistical analysis title
    Seroresponse Difference
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Booster Cohort:- mRNA:AZD1222 (Comparator) v Booster Cohort:- mRNA:AZD1222 (Reference)
    Number of subjects included in analysis
    560
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [109]
    Method
    Parameter type
    Seroresponse difference
    Point estimate
    14.64
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    6.36
         upper limit
    22.64
    Notes
    [109] - Non-inferiority was demonstrated if the lower limit of the 2-sided 95% CI rate difference in seroresponse between the comparator group and reference group was > or =-10%.

    Secondary: GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Primary Vaccination Cohort:- AZD2816 (4) and Primary Vaccination Cohort:- AZD1222 (4) on Day 29

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    End point title
    GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Primary Vaccination Cohort:- AZD2816 (4) and Primary Vaccination Cohort:- AZD1222 (4) on Day 29 [110]
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Primary Vaccination Cohort:- AZD2816 (4) is the comparator group and Primary Vaccination Cohort:- AZD1222 (4) is the reference group, both compared for response against B.1.351 variant. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    28 days after first dose (Day 29)
    Notes
    [110] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Primary Vaccination Cohort:- AZD1222 (4) Primary Vaccination Cohort:- AZD2816 (4)
    Number of subjects analysed
    361
    357
    Units: 1/dilution
        geometric mean (confidence interval 95%)
    233.65 (226.02 to 241.54)
    398.60 (381.99 to 415.95)
    Statistical analysis title
    GMT Ratio
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Primary Vaccination Cohort:- AZD2816 (4) v Primary Vaccination Cohort:- AZD1222 (4)
    Number of subjects included in analysis
    718
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [111]
    Method
    Parameter type
    GMT ratio
    Point estimate
    1.71
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.62
         upper limit
    1.8
    Notes
    [111] - Noninferiority was demonstrated if the lower limit of the 2-sided 95% CI of the GMT ratio of the comparator group and reference group was > 0.67.

    Secondary: GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Primary Vaccination Cohort:- AZD2816 (4) and the Original Wuhan-Hu-1 Strain Elicited by Primary Vaccination Cohort:- AZD1222 (4) on Day 29

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    End point title
    GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Primary Vaccination Cohort:- AZD2816 (4) and the Original Wuhan-Hu-1 Strain Elicited by Primary Vaccination Cohort:- AZD1222 (4) on Day 29 [112]
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. GMT was calculated as antilogarithm of Σ(log base 2 transformed titre/n), i.e. as anti-logarithm transformation of the mean of log-transformed titre, where 'n' was the number of participants with titre information. Primary Vaccination Cohort:- AZD2816 (4) with response against B.1.351 variant is comparator group and Primary Vaccination Cohort:- AZD1222 (4) with response against the original Wuhan-Hu-1 strain is reference group. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    28 days after first dose (Day 29)
    Notes
    [112] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Primary Vaccination Cohort:- AZD1222 (4) Primary Vaccination Cohort:- AZD2816 (4)
    Number of subjects analysed
    361
    357
    Units: 1/dilution
        geometric mean (confidence interval 95%)
    433.42 (398.43 to 471.48)
    364.20 (330.75 to 401.04)
    Statistical analysis title
    GMT Ratio
    Statistical analysis description
    The analyses were derived using analysis of covariance (ANCOVA).
    Comparison groups
    Primary Vaccination Cohort:- AZD2816 (4) v Primary Vaccination Cohort:- AZD1222 (4)
    Number of subjects included in analysis
    718
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [113]
    Method
    Parameter type
    GMT ratio
    Point estimate
    0.84
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.74
         upper limit
    0.96
    Notes
    [113] - Noninferiority was demonstrated if the lower limit of the 2-sided 95% CI of the GMT ratio of the comparator group and reference group was > 0.67.

    Secondary: GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) and the Original Wuhan-Hu-1 Strain Elicited by Primary Vaccination Cohort:- AZD1222 (4) on Day 29

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    End point title
    GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) and the Original Wuhan-Hu-1 Strain Elicited by Primary Vaccination Cohort:- AZD1222 (4) on Day 29 [114]
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. GMT was calculated as antilogarithm of Σ(log base 2 transformed titre/n), i.e. as anti-logarithm transformation of mean of log-transformed titre, where 'n' was number of participants with titre information. Primary Vaccination Cohort:-AZD1222+AZD2816(4) with response against B.1.351 variant is comparator group and Primary Vaccination Cohort:-AZD1222(4) with response against the original Wuhan-Hu-1 strain is reference group. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    28 days after first dose (Day 29)
    Notes
    [114] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Primary Vaccination Cohort:- AZD1222 (4) Primary Vaccination Cohort:- AZD1222 + AZD2816 (4)
    Number of subjects analysed
    361
    357
    Units: 1/dilution
        geometric mean (confidence interval 95%)
    525.20 (481.75 to 572.58)
    261.55 (240.05 to 284.97)
    Statistical analysis title
    GMT Ratio
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) v Primary Vaccination Cohort:- AZD1222 (4)
    Number of subjects included in analysis
    718
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [115]
    Method
    Parameter type
    GMT ratio
    Point estimate
    0.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.44
         upper limit
    0.56
    Notes
    [115] - Noninferiority was demonstrated if the lower limit of the 2-sided 95% CI of the GMT ratio of the comparator group and reference group was > 0.67.

    Secondary: GMT of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Primary Vaccination Cohort:- AZD2816 (4) and Primary Vaccination Cohort:- AZD1222 (4) on Day 29

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    End point title
    GMT of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Primary Vaccination Cohort:- AZD2816 (4) and Primary Vaccination Cohort:- AZD1222 (4) on Day 29 [116]
    End point description
    The SARS-CoV-2 nAb were measured by pseudoneutralisation assay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Primary Vaccination Cohort:- AZD2816 (4) is the comparator group and Primary Vaccination Cohort:- AZD1222 (4) is the reference group, both compared for response against the original Wuhan-Hu-1 strain. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    28 days after first dose (Day 29)
    Notes
    [116] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Primary Vaccination Cohort:- AZD1222 (4) Primary Vaccination Cohort:- AZD2816 (4)
    Number of subjects analysed
    361
    357
    Units: 1/dilution
        geometric mean (confidence interval 95%)
    471.69 (420.91 to 528.59)
    177.02 (160.25 to 195.53)
    Statistical analysis title
    GMT Ratio
    Statistical analysis description
    The analyses were derived using ANCOVA.
    Comparison groups
    Primary Vaccination Cohort:- AZD2816 (4) v Primary Vaccination Cohort:- AZD1222 (4)
    Number of subjects included in analysis
    718
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [117]
    Method
    Parameter type
    GMT ratio
    Point estimate
    0.38
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.32
         upper limit
    0.44
    Notes
    [117] - Noninferiority was demonstrated if the lower limit of the 2-sided 95% CI of the GMT ratio of the comparator group and reference group was > 0.67.

    Secondary: GMT of ChAdOx1 nAb in Primary Vaccination Cohorts and Following a Booster Dose of AZD2816

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    End point title
    GMT of ChAdOx1 nAb in Primary Vaccination Cohorts and Following a Booster Dose of AZD2816 [118]
    End point description
    Chimpanzee adenovirus Ox1 (ChAdOx1) vector nAb were measured by neutralisation assay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    Booster Cohorts: 28 days after booster dose (Day 29) and Primary Vaccination Cohorts: 28 days after the second dose (Day 57 for 4-week dosing interval cohorts and Day 113 for 12-week dosing interval cohort)
    Notes
    [118] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Primary Vaccination Cohort:- AZD1222 (4) Primary Vaccination Cohort:- AZD2816 (4) Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) Primary Vaccination Cohort:- AZD2816 (12) Booster Cohort:- AZD1222:AZD2816 Booster Cohort:- mRNA:AZD2816
    Number of subjects analysed
    232
    225
    217
    7
    320
    277
    Units: 1/dilution
        geometric mean (confidence interval 95%)
    2369.38 (2165.69 to 2592.23)
    1640.99 (1510.43 to 1782.83)
    1656.53 (1529.80 to 1793.75)
    2082.82 (787.88 to 5506.10)
    3830.85 (3574.28 to 4105.83)
    811.44 (721.11 to 913.08)
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Seroresponse of ChAdOx1 nAb in Primary Vaccination Cohorts and Following a Booster Dose of AZD2816

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    End point title
    Percentage of Participants With Seroresponse of ChAdOx1 nAb in Primary Vaccination Cohorts and Following a Booster Dose of AZD2816 [119]
    End point description
    Chimpanzee adenovirus Ox1 vector nAb were measured by neutralisation assay. Seroresponse was defined as >= 4-fold increase in the GMT of nAb from baseline. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    Booster Cohorts: 28 days after booster dose (Day 29) and Primary Vaccination Cohorts: 28 days after the second dose (Day 57 for 4-week dosing interval cohorts and Day 113 for 12-week dosing interval cohort)
    Notes
    [119] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Primary Vaccination Cohort:- AZD1222 (4) Primary Vaccination Cohort:- AZD2816 (4) Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) Primary Vaccination Cohort:- AZD2816 (12) Booster Cohort:- AZD1222:AZD2816 Booster Cohort:- mRNA:AZD2816
    Number of subjects analysed
    227
    224
    209
    7
    319
    275
    Units: Percentage of participants
        number (confidence interval 95%)
    89.43 (84.68 to 93.11)
    93.30 (89.20 to 96.20)
    91.39 (86.73 to 94.82)
    85.71 (42.13 to 99.64)
    62.07 (56.50 to 67.42)
    87.64 (83.15 to 91.28)
    No statistical analyses for this end point

    Secondary: GMT of SARS-CoV-2 Spike Protein Binding Antibodies in Primary Vaccination Cohorts and Booster Cohorts

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    End point title
    GMT of SARS-CoV-2 Spike Protein Binding Antibodies in Primary Vaccination Cohorts and Booster Cohorts
    End point description
    The SARS-CoV-2 spike (S)-protein binding antibodies were measured by multiplexed immunoassay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    Booster Cohorts: 28 days after booster dose (Day 29) and Primary Vaccination Cohorts: 28 days after the second dose (Day 57 for 4-week dosing interval cohorts and Day 113 for 12-week dosing interval cohort)
    End point values
    Primary Vaccination Cohort:- AZD1222 (4) Primary Vaccination Cohort:- AZD2816 (4) Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) Primary Vaccination Cohort:- AZD2816 (12) Booster Cohort:- AZD1222:AZD1222 Booster Cohort:- AZD1222:AZD2816 Booster Cohort:- mRNA:AZD1222 Booster Cohort:- mRNA:AZD2816
    Number of subjects analysed
    347
    341
    333
    157
    329
    320
    279
    279
    Units: 1/dilution
    geometric mean (confidence interval 95%)
        B.1.351
    28618.30 (25758.25 to 31795.92)
    29325.20 (26677.38 to 32235.81)
    23119.62 (20524.01 to 26043.50)
    43047.62 (37018.88 to 50058.17)
    14382.37 (13365.31 to 15476.82)
    16561.93 (15630.53 to 17548.83)
    45587.11 (42653.03 to 48723.02)
    65705.69 (62446.19 to 69135.33)
        Wuhan-Hu-1
    59332.38 (53222.73 to 66143.39)
    21570.78 (19701.94 to 23616.89)
    38145.52 (33713.61 to 43160.03)
    25672.89 (21953.82 to 30021.99)
    34214.45 (31691.34 to 36938.43)
    29254.7 (27650.20 to 30952.30)
    106061.18 (98649.55 to 114029.66)
    113358.29 (107769.93 to 119236.43)
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Seroresponse of SARS-CoV-2 Spike Protein Binding Antibodies in Primary Vaccination Cohorts and Booster Cohorts

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    End point title
    Percentage of Participants With Seroresponse of SARS-CoV-2 Spike Protein Binding Antibodies in Primary Vaccination Cohorts and Booster Cohorts
    End point description
    The SARS-CoV-2 S-protein binding antibodies were measured by multiplexed immunoassay. Seroresponse was defined as >= 4-fold increase in the GMT of S-protein binding antibodies from baseline. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    Booster Cohorts: 28 days after booster dose (Day 29) and Primary Vaccination Cohorts: 28 days after the second dose (Day 57 for 4-week dosing interval cohorts and Day 113 for 12-week dosing interval cohort)
    End point values
    Primary Vaccination Cohort:- AZD1222 (4) Primary Vaccination Cohort:- AZD2816 (4) Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) Primary Vaccination Cohort:- AZD2816 (12) Booster Cohort:- AZD1222:AZD1222 Booster Cohort:- AZD1222:AZD2816 Booster Cohort:- mRNA:AZD1222 Booster Cohort:- mRNA:AZD2816
    Number of subjects analysed
    345
    341
    333
    156
    329
    320
    279
    278
    Units: Percentage of participants
    number (confidence interval 95%)
        B.1.351
    97.10 (94.73 to 98.60)
    97.36 (95.05 to 98.79)
    93.99 (90.88 to 96.29)
    98.08 (94.48 to 99.60)
    70.82 (65.58 to 75.68)
    75.94 (70.87 to 80.52)
    30.47 (25.12 to 36.23)
    51.08 (45.04 to 57.10)
        Wuhan-Hu-1
    97.68 (95.48 to 98.99)
    95.01 (92.14 to 97.07)
    94.29 (91.23 to 96.53)
    96.15 (91.82 to 98.58)
    67.78 (62.44 to 72.80)
    64.69 (59.18 to 69.92)
    36.56 (30.90 to 42.51)
    41.01 (35.17 to 47.04)
    No statistical analyses for this end point

    Secondary: Correlation Between ChAdOx1 nAb and SARS-CoV-2 nAb Titres

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    End point title
    Correlation Between ChAdOx1 nAb and SARS-CoV-2 nAb Titres
    End point description
    The SARS-CoV-2 nAb and ChAdOx1 vector nAb were measured by pseudoneutralisation assay. Correlations were based on log2 titre values and assessed by using Spearman rank correlation for all cohorts except Primary Vaccination Cohort:-AZD2816(12) for which Pearson correlation was used. Correlation coefficient is reported in values from +1 to -1 (+1=perfect association, 0=no association, and -1=perfect negative association). The closer the correlation coefficient is to zero, weaker the association. Seronegative immunogenicity analysis set: all participants who received at least 1 dose of study treatment, had baseline and post-dose antibody measurements, at least 1 post-dose quantifiable serum titre, and no protocol deviations judged to have potential to interfere with the antibody response, were analysed according to treatment actually received, and were seronegative at baseline. The number of subjects analyzed denotes those participants who were evaluable at the specified time frame.
    End point type
    Secondary
    End point timeframe
    Booster Cohorts: 28 days after booster dose (Day 29) and Primary Vaccination Cohorts: 28 days after the second dose (Day 57 for 4-week dosing interval cohorts and Day 113 for 12-week dosing interval cohort)
    End point values
    Primary Vaccination Cohort:- AZD1222 (4) Primary Vaccination Cohort:- AZD2816 (4) Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) Primary Vaccination Cohort:- AZD2816 (12) Booster Cohort:- AZD1222:AZD1222 Booster Cohort:- AZD1222:AZD2816 Booster Cohort:- mRNA:AZD1222 Booster Cohort:- mRNA:AZD2816
    Number of subjects analysed
    232
    225
    217
    7
    327
    320
    275
    277
    Units: Correlation coefficient
    number (confidence interval 95%)
        B.1.351
    -0.1656 (-0.29 to -0.04)
    -0.0536 (-0.18 to 0.08)
    -0.0783 (-0.21 to 0.06)
    0.0253 (-0.74 to 0.76)
    0.2061 (0.10 to 0.31)
    0.2297 (0.12 to 33)
    0.0225 (-0.10 to 0.14)
    -0.0591 (-0.18 to 0.06)
        Wuhan-Hu-1
    -0.1263 (-0.25 to 0.00)
    0.0006 (-0.13 to 0.13)
    -0.0162 (-0.15 to 0.12)
    -0.1460 (-0.81 to 0.69)
    0.1288 (0.02 to 0.23)
    0.1583 (0.05 to 0.26)
    0.0005 (-0.12 to 0.12)
    -0.0534 (-0.17 to 0.06)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    During the 6 months follow-up period after vaccination (vaccines administered on Days 1 and 29 or Day 85 [only for primary vaccination cohorts])
    Adverse event reporting additional description
    Safety analysis set included all participants who received at least 1 dose of study treatment and were analysed according to the treatment actually received.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    25.0
    Reporting groups
    Reporting group title
    Primary Vaccination Cohort:- AZD1222 (4)
    Reporting group description
    Previously unvaccinated participants received IM AZD1222 5*10^10 vp on Days 1 and 29 (4-week dosing interval).

    Reporting group title
    Primary Vaccination Cohort:- AZD2816 (4)
    Reporting group description
    Previously unvaccinated participants received IM AZD2816 5*10^10 vp on Days 1 and 29 (4-week dosing interval).

    Reporting group title
    Primary Vaccination Cohort:- AZD1222 + AZD2816 (4)
    Reporting group description
    Previously unvaccinated participants received IM AZD1222 5*10^10 vp on Day 1 and IM AZD2816 5*10^10 vp on Day 29 (4-week dosing interval).

    Reporting group title
    Booster Cohort:- mRNA:AZD2816
    Reporting group description
    Participants, who previously received 2 doses of approved mRNA based vaccine according to the authorized dose and dosing regimen, with second dose administered at least 90 days prior to study treatment, received booster dose of IM AZD2816 5*10^10 vp on Day 1.

    Reporting group title
    Booster Cohort:- AZD1222:AZD1222
    Reporting group description
    Participants, who previously received 2 doses of AZD1222 vaccine according to the authorized dose and dosing regimen, with second dose administered at least 90 days prior to study treatment, received booster dose of IM AZD1222 5*10^10 vp on Day 1.

    Reporting group title
    Booster Cohort:- AZD1222:AZD2816
    Reporting group description
    Participants, who previously received 2 doses of AZD1222 vaccine according to the authorized dose and dosing regimen, with second dose administered at least 90 days prior to study treatment, received booster dose of IM AZD2816 5*10^10 vp on Day 1.

    Reporting group title
    Booster Cohort:- mRNA:AZD1222
    Reporting group description
    Participants, who previously received 2 doses of approved mRNA based vaccine according to the authorized dose and dosing regimen, with second dose administered at least 90 days prior to study treatment, received booster dose of IM AZD1222 5*10^10 vp on Day 1.

    Reporting group title
    Primary Vaccination Cohort:- AZD2816 (12)
    Reporting group description
    Previously unvaccinated participants received IM AZD2816 5*10^10 vp on Days 1 and 85 (12-week dosing interval).

    </
    Serious adverse events
    Primary Vaccination Cohort:- AZD1222 (4) Primary Vaccination Cohort:- AZD2816 (4) Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) Booster Cohort:- mRNA:AZD2816 Booster Cohort:- AZD1222:AZD1222 Booster Cohort:- AZD1222:AZD2816 Booster Cohort:- mRNA:AZD1222 Primary Vaccination Cohort:- AZD2816 (12)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 409 (0.73%)
    3 / 413 (0.73%)
    5 / 411 (1.22%)
    5 / 323 (1.55%)
    6 / 373 (1.61%)
    8 / 375 (2.13%)
    3 / 322 (0.93%)
    2 / 208 (0.96%)
         number of deaths (all causes)
    1
    0
    0
    0
    0
    1
    0
    0
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Invasive lobular breast carcinoma
         subjects affected / exposed
    0 / 409 (0.00%)
    0 / 413 (0.00%)
    0 / 411 (0.00%)
    0 / 323 (0.00%)
    0 / 373 (0.00%)
    0 / 375 (0.00%)
    1 / 322 (0.31%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myelodysplastic syndrome
         subjects affected / exposed
    0 / 409 (0.00%)
    0 / 413 (0.00%)
    0 / 411 (0.00%)
    0 / 323 (0.00%)
    0 / 373 (0.00%)
    1 / 375 (0.27%)
    0 / 322 (0.00%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatic carcinoma metastatic
         subjects affected / exposed
    0 / 409 (0.00%)
    0 / 413 (0.00%)
    0 / 411 (0.00%)
    0 / 323 (0.00%)
    0 / 373 (0.00%)
    1 / 375 (0.27%)
    0 / 322 (0.00%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Rectal adenocarcinoma1
         subjects affected / exposed
    0 / 409 (0.00%)
    0 / 413 (0.00%)
    0 / 411 (0.00%)
    0 / 323 (0.00%)
    0 / 373 (0.00%)
    0 / 375 (0.00%)
    1 / 322 (0.31%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transitional cell carcinoma
         subjects affected / exposed
    0 / 409 (0.00%)
    0 / 413 (0.00%)
    0 / 411 (0.00%)
    0 / 323 (0.00%)
    1 / 373 (0.27%)
    0 / 375 (0.00%)
    0 / 322 (0.00%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Ankle fracture
         subjects affected / exposed
    0 / 409 (0.00%)
    0 / 413 (0.00%)
    0 / 411 (0.00%)
    0 / 323 (0.00%)
    0 / 373 (0.00%)
    1 / 375 (0.27%)
    0 / 322 (0.00%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    1 / 409 (0.24%)
    0 / 413 (0.00%)
    0 / 411 (0.00%)
    0 / 323 (0.00%)
    0 / 373 (0.00%)
    0 / 375 (0.00%)
    0 / 322 (0.00%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clavicle fracture
         subjects affected / exposed
    0 / 409 (0.00%)
    0 / 413 (0.00%)
    0 / 411 (0.00%)
    0 / 323 (0.00%)
    1 / 373 (0.27%)
    0 / 375 (0.00%)
    0 / 322 (0.00%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    0 / 409 (0.00%)
    1 / 413 (0.24%)
    0 / 411 (0.00%)
    0 / 323 (0.00%)
    0 / 373 (0.00%)
    0 / 375 (0.00%)
    0 / 322 (0.00%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tendon rupture
         subjects affected / exposed
    0 / 409 (0.00%)
    0 / 413 (0.00%)
    1 / 411 (0.24%)
    0 / 323 (0.00%)
    0 / 373 (0.00%)
    0 / 375 (0.00%)
    0 / 322 (0.00%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    1 / 409 (0.24%)
    0 / 413 (0.00%)
    0 / 411 (0.00%)
    0 / 323 (0.00%)
    0 / 373 (0.00%)
    0 / 375 (0.00%)
    0 / 322 (0.00%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute coronary syndrome
         subjects affected / exposed
    0 / 409 (0.00%)
    1 / 413 (0.24%)
    0 / 411 (0.00%)
    0 / 323 (0.00%)
    0 / 373 (0.00%)
    0 / 375 (0.00%)
    0 / 322 (0.00%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinus tachycardia
         subjects affected / exposed
    0 / 409 (0.00%)
    0 / 413 (0.00%)
    0 / 411 (0.00%)
    1 / 323 (0.31%)
    0 / 373 (0.00%)
    0 / 375 (0.00%)
    0 / 322 (0.00%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 409 (0.00%)
    0 / 413 (0.00%)
    0 / 411 (0.00%)
    1 / 323 (0.31%)
    0 / 373 (0.00%)
    0 / 375 (0.00%)
    0 / 322 (0.00%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    0 / 409 (0.00%)
    0 / 413 (0.00%)
    0 / 411 (0.00%)
    1 / 323 (0.31%)
    0 / 373 (0.00%)
    0 / 375 (0.00%)
    0 / 322 (0.00%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Bell's palsy
         subjects affected / exposed
    0 / 409 (0.00%)
    0 / 413 (0.00%)
    0 / 411 (0.00%)
    0 / 323 (0.00%)
    1 / 373 (0.27%)
    0 / 375 (0.00%)
    0 / 322 (0.00%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    0 / 409 (0.00%)
    0 / 413 (0.00%)
    0 / 411 (0.00%)
    0 / 323 (0.00%)
    0 / 373 (0.00%)
    1 / 375 (0.27%)
    0 / 322 (0.00%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetic neuropathy
         subjects affected / exposed
    0 / 409 (0.00%)
    0 / 413 (0.00%)
    0 / 411 (0.00%)
    0 / 323 (0.00%)
    1 / 373 (0.27%)
    0 / 375 (0.00%)
    0 / 322 (0.00%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoglossal nerve paralysis
         subjects affected / exposed
    0 / 409 (0.00%)
    0 / 413 (0.00%)
    0 / 411 (0.00%)
    0 / 323 (0.00%)
    1 / 373 (0.27%)
    0 / 375 (0.00%)
    0 / 322 (0.00%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 409 (0.00%)
    0 / 413 (0.00%)
    1 / 411 (0.24%)
    0 / 323 (0.00%)
    0 / 373 (0.00%)
    0 / 375 (0.00%)
    0 / 322 (0.00%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 409 (0.00%)
    0 / 413 (0.00%)
    0 / 411 (0.00%)
    0 / 323 (0.00%)
    0 / 373 (0.00%)
    1 / 375 (0.27%)
    0 / 322 (0.00%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Gastritis
         subjects affected / exposed
    0 / 409 (0.00%)
    1 / 413 (0.24%)
    0 / 411 (0.00%)
    0 / 323 (0.00%)
    0 / 373 (0.00%)
    0 / 375 (0.00%)
    0 / 322 (0.00%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 409 (0.00%)
    0 / 413 (0.00%)
    0 / 411 (0.00%)
    0 / 323 (0.00%)
    1 / 373 (0.27%)
    0 / 375 (0.00%)
    0 / 322 (0.00%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis
         subjects affected / exposed
    0 / 409 (0.00%)
    0 / 413 (0.00%)
    1 / 411 (0.24%)
    0 / 323 (0.00%)
    1 / 373 (0.27%)
    0 / 375 (0.00%)
    0 / 322 (0.00%)
    0 / 208 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0